Szabolcs Török1 , Gábor Borgulya1, Péter Lobmayer2, Zsuzsanna Jakab1, Dezsö Schuler1 and György Fekete1
(1) Faculty of Medicine, 2nd Department of Paediatrics, National Paediatric Cancer Registry of Hungary, Semmelweis University, Budapest, Hungary
(2) Faculty of Medicine, Institute of Hygiene, Semmelweis University, Budapest, Hungary
(3) 2nd Department of Paediatrics, Semmelweis University, Tüzoltó utca 7-9, H-1094 Budapest, Hungary
Accepted: 22 August 2005
Abstract The incidence of childhood leukaemia in Hungary has yet to be reported, although data are available since the early 70s. The Hungarian data therefore cover the time before and after the Chernobyl nuclear accident (1986). The aim of this study was to assess the effects of the Chernobyl accident on childhood leukaemia incidence in Hungary. A population-based study was carried out using data of the National Paediatric Cancer Registry of Hungary from 1973 to 2002. The total number of cases was 2204. To test the effect of the Chernobyl accident the authors applied a new approach called ‘Hypothesized Impact Period Interpolation’-model, which takes into account the increasing trend of childhood leukaemia incidence and the hypothesized exposure and latency times. The incidence of leukaemia in the age group 0–14 varied between 33.2 and 39.4 per million person-years along the observed 30 year period, and the incidence of childhood leukaemia showed a moderate increase of 0.71% annually (p=0.0105). In the period of the hypothesized impact of the Chernobyl accident the incidence rate was elevated by 2.5% (95% CI: −8.1%; +14.3%), but this change was not statistically significant (p=0.663). The age standardised incidence, the age distribution, the gender ratio, and the magnitude of increasing trend of childhood leukaemia incidence in Hungary were similar to other European countries. Applying the presented interpolation method the authors did not find a statistically significant increase in the leukaemia incidence in the period of the hypothesized impact of the Chernobyl accident.
Keywords Chernobyl fallout - Childhood leukaemia incidence - Hungary - Interpolation model - Radiation risk
Tuesday, April 15, 2008
Childhood central nervous system leukemia: historical perspectives, current therapy, and acute neurological sequelae
Fred H. Laningham1, 5 , Larry E. Kun3, 5, Wilburn E. Reddick2, Robert J. Ogg2, E. Brannon Morris4 and Ching-Hon Pui4, 5
(1) Division of Diagnostic Imaging (MS #210), Department of Radiological Sciences, St. Jude Children’s Research Hospital, 332 N. Lauderdale Street, Memphis, TN 38105-2794, USA
(2) Division of Translational Imaging Research, Department of Radiological Sciences, St. Jude Children’s Research Hospital, Memphis, TN, USA
(3) Division of Radiation Oncology, Department of Radiological Sciences, St. Jude Children’s Research Hospital, Memphis, TN, USA
(4) Department of Oncology, St. Jude Children’s Research Hospital, Memphis, TN, USA
(5) University of Tennessee Health Sciences Center, Memphis, TN, USA
Received: 22 July 2007 Accepted: 25 July 2007 Published online: 9 October 2007
Abstract
Introduction During the past three decades, improvements in the treatment of childhood leukemia have resulted in high cure rates, particularly for acute lymphoblastic leukemia (ALL). Unfortunately, successful therapy has come with a price, as significant morbidity can result from neurological affects which harm the brain and spinal cord. The expectation and hope is that chemotherapy, as a primary means of CNS therapy, will result in acceptable disease control with less CNS morbidity than has been observed with combinations of chemotherapy and radiotherapy over the past several decades.
Methods and results In this review we discuss the poignant, historical aspects of CNS leukemia therapy, outline current methods of systemic and CNS leukemia therapy, and present imaging findings we have encountered in childhood leukemia patients with a variety of acute neurological conditions. A major objective of our research is to understand the neuroimaging correlates of acute and chronic effects of cancer and therapy. Specific features related to CNS leukemia and associated short-term toxicities, both disease- and therapy-related, are emphasized in this review with the specific neuroimaging findings. Specific CNS findings are similarly important when treating acute myelogenous leukemia (AML), and details of leukemic involvement and toxicities are also presented in this entity.
Conclusion Despite contemporary treatment approaches which favor the use of chemotherapy (including intrathecal therapy) over radiotherapy in the treatment of CNS leukemia, children still occasionally experience morbid neurotoxicity. Standard neuroimaging is sufficient to identify a variety of neurotoxic sequelae in children, and often suggest specific etiologies. Specific neuroimaging findings frequently indicate a need to alter antileukemia therapy. It is important to appreciate that intrathecal and high doses of systemic chemotherapy are not innocuous and are associated with acute, specific, recognizable, and often serious neurological consequences.
Keywords Childhood CNS leukemia - Neurotoxicity - Intrathecal therapy - CNS infection - Secondary malignancies - Methotrexate
(1) Division of Diagnostic Imaging (MS #210), Department of Radiological Sciences, St. Jude Children’s Research Hospital, 332 N. Lauderdale Street, Memphis, TN 38105-2794, USA
(2) Division of Translational Imaging Research, Department of Radiological Sciences, St. Jude Children’s Research Hospital, Memphis, TN, USA
(3) Division of Radiation Oncology, Department of Radiological Sciences, St. Jude Children’s Research Hospital, Memphis, TN, USA
(4) Department of Oncology, St. Jude Children’s Research Hospital, Memphis, TN, USA
(5) University of Tennessee Health Sciences Center, Memphis, TN, USA
Received: 22 July 2007 Accepted: 25 July 2007 Published online: 9 October 2007
Abstract
Introduction During the past three decades, improvements in the treatment of childhood leukemia have resulted in high cure rates, particularly for acute lymphoblastic leukemia (ALL). Unfortunately, successful therapy has come with a price, as significant morbidity can result from neurological affects which harm the brain and spinal cord. The expectation and hope is that chemotherapy, as a primary means of CNS therapy, will result in acceptable disease control with less CNS morbidity than has been observed with combinations of chemotherapy and radiotherapy over the past several decades.
Methods and results In this review we discuss the poignant, historical aspects of CNS leukemia therapy, outline current methods of systemic and CNS leukemia therapy, and present imaging findings we have encountered in childhood leukemia patients with a variety of acute neurological conditions. A major objective of our research is to understand the neuroimaging correlates of acute and chronic effects of cancer and therapy. Specific features related to CNS leukemia and associated short-term toxicities, both disease- and therapy-related, are emphasized in this review with the specific neuroimaging findings. Specific CNS findings are similarly important when treating acute myelogenous leukemia (AML), and details of leukemic involvement and toxicities are also presented in this entity.
Conclusion Despite contemporary treatment approaches which favor the use of chemotherapy (including intrathecal therapy) over radiotherapy in the treatment of CNS leukemia, children still occasionally experience morbid neurotoxicity. Standard neuroimaging is sufficient to identify a variety of neurotoxic sequelae in children, and often suggest specific etiologies. Specific neuroimaging findings frequently indicate a need to alter antileukemia therapy. It is important to appreciate that intrathecal and high doses of systemic chemotherapy are not innocuous and are associated with acute, specific, recognizable, and often serious neurological consequences.
Keywords Childhood CNS leukemia - Neurotoxicity - Intrathecal therapy - CNS infection - Secondary malignancies - Methotrexate
Adjuvante endokrine Therapie des Mammakarzinoms
T. Cordes1, A. Schutze-Mosgau1, D. Finas1, M. Friedrich1, K. Diedrich1 und D. Diesing1, 2
(1) Klinik für Frauenheilkunde und Geburtshilfe, Universitätsklinikum Schleswig-Holstein, Campus Lübeck,
(2) Klinik für Frauenheilkunde und Geburtshilfe, Universitätsklinikum Schleswig-Holstein, Campus Lübeck, Ratzeburger Allee 160, 23538 Lübeck
Online publiziert: 19. April 2005
Zusammenfassung Die endokrine Therapie ist einer der Hauptpfeiler in der adjuvanten Situation des primären rezeptorpositiven Mammakarzinoms. In der postmenopausalen Adjuvans ist Tamoxifen in zahlreichen Studien mit hohen Patientenzahlen über Jahre untersucht worden. Es ist bisher Goldstandard. Die in den letzten Jahren veröffentlichten Studienergebnisse mit Aromatasehemmern der 3. Generation in der adjuvanten Therapie haben jedoch dazu geführt, dass ein Umdenken der bisherigen Therapie mit Tamoxifen stattfinden könnte. Insbesondere die letzten veröffentlichten Ergebnisse der International Exemestane Study Group und der ATAC-Trialist Group sprechen für einen Vorteil in der sequenziellen Behandlung und in der 5-Jahres-Therapie von Beginn an mit Aromatasehemmern. Es zeigen sich Hinweise auf eine Verlängerung des krankheitsfreien Intervalls, eine Reduktion der kontralateralen Rezidive und eine Verbesserung hinsichtlich des Zeitraums des Auftretens distanter Metastasierung. Die Nachbeobachtungszeit der Studien muss abgewartet werden, bis man endgültige Aussagen über Nebenwirkungsprofile treffen kann. Die aktuellen Studienergebnisse und Konsensuserklärungen werden zusammengefasst und die daraus resultierenden Konsequenzen für die adjuvante Therapie in der derzeitigen Situation dargelegt.
Schlüsselwörter Tamoxifen - Aromatasehemmer der 3. Generation - Mammakarzinom - Exemestane Study Group - ATAC-Trialist Group
--------------------------------------------------------------------------------
Adjuvant endocrine therapy for breast cancer
Updated aspects from new study results, ASCO 2004, and the St. Gallen consensus statements of 2005
Abstract Endocrine treatment is one of the main therapy options in the adjuvant setting of receptor-positive breast cancer. Many long-term studies have investigated a high number of postmenopausal patients receiving adjuvant tamoxifen therapy. Tamoxifen has been the golden standard. Throughout the last few years interesting results on third-generation aromatase inhibitors (AI) in the adjuvant setting have been published. Tamoxifen has not lost its position, but new results of the IES 031 and the ATAC trial have shown a better outcome in sequential or primary adjuvant therapy with AIs regarding disease-free survival, contralateral breast cancer events, and the time to distant recurrence. Longer follow-ups of ongoing studies are needed to evaluate overall survival and long-term side effects. This is a review of the latest results and consensus statements regarding consequences for adjuvant therapy.
Keywords Tamoxifen - Third-generation aromatase inhibitors - Breast cancer - Exemestane Study Group - ATAC Trialist Group
(1) Klinik für Frauenheilkunde und Geburtshilfe, Universitätsklinikum Schleswig-Holstein, Campus Lübeck,
(2) Klinik für Frauenheilkunde und Geburtshilfe, Universitätsklinikum Schleswig-Holstein, Campus Lübeck, Ratzeburger Allee 160, 23538 Lübeck
Online publiziert: 19. April 2005
Zusammenfassung Die endokrine Therapie ist einer der Hauptpfeiler in der adjuvanten Situation des primären rezeptorpositiven Mammakarzinoms. In der postmenopausalen Adjuvans ist Tamoxifen in zahlreichen Studien mit hohen Patientenzahlen über Jahre untersucht worden. Es ist bisher Goldstandard. Die in den letzten Jahren veröffentlichten Studienergebnisse mit Aromatasehemmern der 3. Generation in der adjuvanten Therapie haben jedoch dazu geführt, dass ein Umdenken der bisherigen Therapie mit Tamoxifen stattfinden könnte. Insbesondere die letzten veröffentlichten Ergebnisse der International Exemestane Study Group und der ATAC-Trialist Group sprechen für einen Vorteil in der sequenziellen Behandlung und in der 5-Jahres-Therapie von Beginn an mit Aromatasehemmern. Es zeigen sich Hinweise auf eine Verlängerung des krankheitsfreien Intervalls, eine Reduktion der kontralateralen Rezidive und eine Verbesserung hinsichtlich des Zeitraums des Auftretens distanter Metastasierung. Die Nachbeobachtungszeit der Studien muss abgewartet werden, bis man endgültige Aussagen über Nebenwirkungsprofile treffen kann. Die aktuellen Studienergebnisse und Konsensuserklärungen werden zusammengefasst und die daraus resultierenden Konsequenzen für die adjuvante Therapie in der derzeitigen Situation dargelegt.
Schlüsselwörter Tamoxifen - Aromatasehemmer der 3. Generation - Mammakarzinom - Exemestane Study Group - ATAC-Trialist Group
--------------------------------------------------------------------------------
Adjuvant endocrine therapy for breast cancer
Updated aspects from new study results, ASCO 2004, and the St. Gallen consensus statements of 2005
Abstract Endocrine treatment is one of the main therapy options in the adjuvant setting of receptor-positive breast cancer. Many long-term studies have investigated a high number of postmenopausal patients receiving adjuvant tamoxifen therapy. Tamoxifen has been the golden standard. Throughout the last few years interesting results on third-generation aromatase inhibitors (AI) in the adjuvant setting have been published. Tamoxifen has not lost its position, but new results of the IES 031 and the ATAC trial have shown a better outcome in sequential or primary adjuvant therapy with AIs regarding disease-free survival, contralateral breast cancer events, and the time to distant recurrence. Longer follow-ups of ongoing studies are needed to evaluate overall survival and long-term side effects. This is a review of the latest results and consensus statements regarding consequences for adjuvant therapy.
Keywords Tamoxifen - Third-generation aromatase inhibitors - Breast cancer - Exemestane Study Group - ATAC Trialist Group
Childhood Cancer and Social Contact: the Role of Paternal Occupation (United Kingdom)*
Nicola T. Fear1 , Jill Simpson2, Eve Roman2 and behalf of the United Kingdom Childhood Cancer Study Investigators
(1) Academic Centre for Defence Mental Health, Institute of Psychiatry, King’s College London, Weston Education Centre, Cutcombe Road, SE5 9RJ London, UK
(2) Leukaemia Research Fund, Epidemiology and Genetics Unit, Department of Health Sciences, University of York Seebohm Rowntree Building, University of York, YO10 5DD York, UK
Received: 15 April 2005 Accepted: 02 June 2005
Abstract Objective: To investigate the relationship between childhood cancer (particularly leukaemia) and paternal occupational social contact (a proxy for potential exposure to infections) using the UK Childhood Cancer Study.
Methods: Using a national population-based case–control study, self-reported occupational data from fathers of 3596 children diagnosed with cancer between 1991 and 1996 under 15 years of age (cases) and fathers of 7011 children without cancer (controls) were analysed. Associations were assessed using odds ratios (OR) calculated by time of exposure (birth, diagnosis), diagnostic group (all cancers, leukaemia, acute lymphoblastic leukaemia (ALL), central nervous system tumours, other cancers), level of occupational social contact (high, medium, low), urban–rural status at diagnosis and occupational title.
Results: From 371 occupations, 75 (20%) were classified as having high levels of occupational social contact, 31 (8%) as medium and the remaining 265 (71%) as low. No associations were apparent for fathers’ occupational social contact overall, for any time period or diagnostic group. OR for leukaemia and high levels of paternal occupational social contact at birth and diagnosis being 1.02 (95% confidence interval (CI) = 0.88–1.18) and 0.91 (95% CI = 0.79–1.06), respectively. Analyses by urban–rural status at diagnosis and by occupational title revealed no notable associations.
Conclusions: The analyses of paternal occupational histories do not support the suggested association between high levels of paternal occupational social contact and an increased risk of childhood leukaemia. However, the role of participation bias should not be discounted.
Keywords case–control study - childhood cancer - leukaemia - paternal occupation - social contact
(1) Academic Centre for Defence Mental Health, Institute of Psychiatry, King’s College London, Weston Education Centre, Cutcombe Road, SE5 9RJ London, UK
(2) Leukaemia Research Fund, Epidemiology and Genetics Unit, Department of Health Sciences, University of York Seebohm Rowntree Building, University of York, YO10 5DD York, UK
Received: 15 April 2005 Accepted: 02 June 2005
Abstract Objective: To investigate the relationship between childhood cancer (particularly leukaemia) and paternal occupational social contact (a proxy for potential exposure to infections) using the UK Childhood Cancer Study.
Methods: Using a national population-based case–control study, self-reported occupational data from fathers of 3596 children diagnosed with cancer between 1991 and 1996 under 15 years of age (cases) and fathers of 7011 children without cancer (controls) were analysed. Associations were assessed using odds ratios (OR) calculated by time of exposure (birth, diagnosis), diagnostic group (all cancers, leukaemia, acute lymphoblastic leukaemia (ALL), central nervous system tumours, other cancers), level of occupational social contact (high, medium, low), urban–rural status at diagnosis and occupational title.
Results: From 371 occupations, 75 (20%) were classified as having high levels of occupational social contact, 31 (8%) as medium and the remaining 265 (71%) as low. No associations were apparent for fathers’ occupational social contact overall, for any time period or diagnostic group. OR for leukaemia and high levels of paternal occupational social contact at birth and diagnosis being 1.02 (95% confidence interval (CI) = 0.88–1.18) and 0.91 (95% CI = 0.79–1.06), respectively. Analyses by urban–rural status at diagnosis and by occupational title revealed no notable associations.
Conclusions: The analyses of paternal occupational histories do not support the suggested association between high levels of paternal occupational social contact and an increased risk of childhood leukaemia. However, the role of participation bias should not be discounted.
Keywords case–control study - childhood cancer - leukaemia - paternal occupation - social contact
Adjuvante endokrine Therapie des Mammakarzinoms
T. Cordes1, A. Schutze-Mosgau1, D. Finas1, M. Friedrich1, K. Diedrich1 und D. Diesing1, 2
(1) Klinik für Frauenheilkunde und Geburtshilfe, Universitätsklinikum Schleswig-Holstein, Campus Lübeck,
(2) Klinik für Frauenheilkunde und Geburtshilfe, Universitätsklinikum Schleswig-Holstein, Campus Lübeck, Ratzeburger Allee 160, 23538 Lübeck
Online publiziert: 19. April 2005
Zusammenfassung Die endokrine Therapie ist einer der Hauptpfeiler in der adjuvanten Situation des primären rezeptorpositiven Mammakarzinoms. In der postmenopausalen Adjuvans ist Tamoxifen in zahlreichen Studien mit hohen Patientenzahlen über Jahre untersucht worden. Es ist bisher Goldstandard. Die in den letzten Jahren veröffentlichten Studienergebnisse mit Aromatasehemmern der 3. Generation in der adjuvanten Therapie haben jedoch dazu geführt, dass ein Umdenken der bisherigen Therapie mit Tamoxifen stattfinden könnte. Insbesondere die letzten veröffentlichten Ergebnisse der International Exemestane Study Group und der ATAC-Trialist Group sprechen für einen Vorteil in der sequenziellen Behandlung und in der 5-Jahres-Therapie von Beginn an mit Aromatasehemmern. Es zeigen sich Hinweise auf eine Verlängerung des krankheitsfreien Intervalls, eine Reduktion der kontralateralen Rezidive und eine Verbesserung hinsichtlich des Zeitraums des Auftretens distanter Metastasierung. Die Nachbeobachtungszeit der Studien muss abgewartet werden, bis man endgültige Aussagen über Nebenwirkungsprofile treffen kann. Die aktuellen Studienergebnisse und Konsensuserklärungen werden zusammengefasst und die daraus resultierenden Konsequenzen für die adjuvante Therapie in der derzeitigen Situation dargelegt.
Schlüsselwörter Tamoxifen - Aromatasehemmer der 3. Generation - Mammakarzinom - Exemestane Study Group - ATAC-Trialist Group
--------------------------------------------------------------------------------
Adjuvant endocrine therapy for breast cancer
Updated aspects from new study results, ASCO 2004, and the St. Gallen consensus statements of 2005
Abstract Endocrine treatment is one of the main therapy options in the adjuvant setting of receptor-positive breast cancer. Many long-term studies have investigated a high number of postmenopausal patients receiving adjuvant tamoxifen therapy. Tamoxifen has been the golden standard. Throughout the last few years interesting results on third-generation aromatase inhibitors (AI) in the adjuvant setting have been published. Tamoxifen has not lost its position, but new results of the IES 031 and the ATAC trial have shown a better outcome in sequential or primary adjuvant therapy with AIs regarding disease-free survival, contralateral breast cancer events, and the time to distant recurrence. Longer follow-ups of ongoing studies are needed to evaluate overall survival and long-term side effects. This is a review of the latest results and consensus statements regarding consequences for adjuvant therapy.
Keywords Tamoxifen - Third-generation aromatase inhibitors - Breast cancer - Exemestane Study Group - ATAC Trialist Group
(1) Klinik für Frauenheilkunde und Geburtshilfe, Universitätsklinikum Schleswig-Holstein, Campus Lübeck,
(2) Klinik für Frauenheilkunde und Geburtshilfe, Universitätsklinikum Schleswig-Holstein, Campus Lübeck, Ratzeburger Allee 160, 23538 Lübeck
Online publiziert: 19. April 2005
Zusammenfassung Die endokrine Therapie ist einer der Hauptpfeiler in der adjuvanten Situation des primären rezeptorpositiven Mammakarzinoms. In der postmenopausalen Adjuvans ist Tamoxifen in zahlreichen Studien mit hohen Patientenzahlen über Jahre untersucht worden. Es ist bisher Goldstandard. Die in den letzten Jahren veröffentlichten Studienergebnisse mit Aromatasehemmern der 3. Generation in der adjuvanten Therapie haben jedoch dazu geführt, dass ein Umdenken der bisherigen Therapie mit Tamoxifen stattfinden könnte. Insbesondere die letzten veröffentlichten Ergebnisse der International Exemestane Study Group und der ATAC-Trialist Group sprechen für einen Vorteil in der sequenziellen Behandlung und in der 5-Jahres-Therapie von Beginn an mit Aromatasehemmern. Es zeigen sich Hinweise auf eine Verlängerung des krankheitsfreien Intervalls, eine Reduktion der kontralateralen Rezidive und eine Verbesserung hinsichtlich des Zeitraums des Auftretens distanter Metastasierung. Die Nachbeobachtungszeit der Studien muss abgewartet werden, bis man endgültige Aussagen über Nebenwirkungsprofile treffen kann. Die aktuellen Studienergebnisse und Konsensuserklärungen werden zusammengefasst und die daraus resultierenden Konsequenzen für die adjuvante Therapie in der derzeitigen Situation dargelegt.
Schlüsselwörter Tamoxifen - Aromatasehemmer der 3. Generation - Mammakarzinom - Exemestane Study Group - ATAC-Trialist Group
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Adjuvant endocrine therapy for breast cancer
Updated aspects from new study results, ASCO 2004, and the St. Gallen consensus statements of 2005
Abstract Endocrine treatment is one of the main therapy options in the adjuvant setting of receptor-positive breast cancer. Many long-term studies have investigated a high number of postmenopausal patients receiving adjuvant tamoxifen therapy. Tamoxifen has been the golden standard. Throughout the last few years interesting results on third-generation aromatase inhibitors (AI) in the adjuvant setting have been published. Tamoxifen has not lost its position, but new results of the IES 031 and the ATAC trial have shown a better outcome in sequential or primary adjuvant therapy with AIs regarding disease-free survival, contralateral breast cancer events, and the time to distant recurrence. Longer follow-ups of ongoing studies are needed to evaluate overall survival and long-term side effects. This is a review of the latest results and consensus statements regarding consequences for adjuvant therapy.
Keywords Tamoxifen - Third-generation aromatase inhibitors - Breast cancer - Exemestane Study Group - ATAC Trialist Group
Adjuvante Chemotherapie beim Mammakarzinom
V. Möbus1, 3 und R. Kreienberg2
(1) Frauenklinik, Städtisches Klinikum Frankfurt,
(2) Universitätsfrauenklinik Ulm,
(3) Frauenklinik, Städtisches Klinikum, Gotenstraße 6–8, 65929 Frankfurt
Online publiziert: 20. April 2005
Zusammenfassung Die Effektivität der adjuvanten Chemotherapie wie der antihormonellen Therapie sind in der letzten Dekade entscheidend verbessert worden. Sequenzielle chemoendokrine Therapien haben zu einer zusätzlichen Wirkungssteigerung bei hormonrezeptorpositiven Patientinnen geführt.
Während CMF und anthrazyklinhaltige Schemata schon lange routinemäßig eingesetzt werden, ist das optimale anthrazyklinhaltige Regime durch St. Gallen 2005 erstmals klar benannt worden (6× FEC oder FAC). Nach Datenlage verfügen wir mittlerweile über 4 Wirksamkeitsstufen der adjuvanten Chemotherapie (4× AC oder 6× CMF <6× FEC(FAC) < taxanhaltige Regime < dosisdichte Regime). Dieser Zugewinn durch die Hinzunahme neuer Substanzen oder die Änderung des schedule (dosisdichte Therapie) ist in randomisierten Studien belegt.
Kontrovers diskutiert wird, ob es hochhormonrezeptorpositive Patientinnen in der mittleren Risikosituation gibt, bei denen die alleinige antihormonelle Therapie eine Alternative zur sequenziellen chemoendokrinen Therapie darstellen kann. Dies impliziert weitreichende Konsequenzen hinsichtlich der Therapiekosten, der Therapiedauer, dem Nebenwirkungsspektrum und noch mehr als zuvor der Aufklärung und der geeigneten Selektion der Patientinnen.
Schlüsselwörter Mammakarzinom - Adjuvante Therapie - Konsensuskonferenz St. Gallen 2005 - Anthrazykline - Taxane
--------------------------------------------------------------------------------
Adjuvant chemotherapy for breast cancer
Abstract The efficacy of both adjuvant chemotherapy and hormonal therapy in breast cancer has improved markedly in the past decade. With combined chemo-endocrine therapy, a further improvement in efficacy can be achieved for hormone-receptor positive patients.
Although CMF (cyclophosphamide, methotrexate and fluorouracil) and anthracycline-containing regimens have long been part of the clinical routine in adjuvant chemotherapy, the optimal anthracycline-containing regimens to date appear to be the three agent combinations FEC or FAC given over six cycles (St. Gallen Consensus Conference 2005). Taxane-containing and dose-dense regimens are new chemotherapy concepts that have emerged in the last few years. From large, comparative chemotherapy trials, the efficacy of common chemotherapy regimens can be described as follows: four cycles of adriamycin-cyclophosphamide (AC) is equivalent to six cycles of cyclophosphamide-methotrexate-fluorouracil (CMF) and both are less efficacious than six cycles of fluorouracil-epirubicin/adriamycin-cyclophosphamide (FEC or FAC), which in turn is less efficacious than taxane-containing regimens. A final improvement in efficacy, also over standard taxane-containing regimens, can be achieved with dose-dense regimens. In other words, 4×AC=6×CMF<6×FEC or FACmoderate risk category with highly endocrine responsive tumors) may be adequately treated with hormone therapy alone is ongoing.
This has widespread implications and consequences for therapy costs, therapy duration, and side effect profile or therapeutic index, which must also be considered when deciding on adjuvant therapy. More than ever before, risk-benefit analysis and individualized patient therapy is of the utmost importance.
Keywords Breast cancer - Adjuvant therapy - Consensus Conference St. Gallen 2005 - Anthracyclines - Taxanes
--------------------------------------------------------------------------------
(1) Frauenklinik, Städtisches Klinikum Frankfurt,
(2) Universitätsfrauenklinik Ulm,
(3) Frauenklinik, Städtisches Klinikum, Gotenstraße 6–8, 65929 Frankfurt
Online publiziert: 20. April 2005
Zusammenfassung Die Effektivität der adjuvanten Chemotherapie wie der antihormonellen Therapie sind in der letzten Dekade entscheidend verbessert worden. Sequenzielle chemoendokrine Therapien haben zu einer zusätzlichen Wirkungssteigerung bei hormonrezeptorpositiven Patientinnen geführt.
Während CMF und anthrazyklinhaltige Schemata schon lange routinemäßig eingesetzt werden, ist das optimale anthrazyklinhaltige Regime durch St. Gallen 2005 erstmals klar benannt worden (6× FEC oder FAC). Nach Datenlage verfügen wir mittlerweile über 4 Wirksamkeitsstufen der adjuvanten Chemotherapie (4× AC oder 6× CMF <6× FEC(FAC) < taxanhaltige Regime < dosisdichte Regime). Dieser Zugewinn durch die Hinzunahme neuer Substanzen oder die Änderung des schedule (dosisdichte Therapie) ist in randomisierten Studien belegt.
Kontrovers diskutiert wird, ob es hochhormonrezeptorpositive Patientinnen in der mittleren Risikosituation gibt, bei denen die alleinige antihormonelle Therapie eine Alternative zur sequenziellen chemoendokrinen Therapie darstellen kann. Dies impliziert weitreichende Konsequenzen hinsichtlich der Therapiekosten, der Therapiedauer, dem Nebenwirkungsspektrum und noch mehr als zuvor der Aufklärung und der geeigneten Selektion der Patientinnen.
Schlüsselwörter Mammakarzinom - Adjuvante Therapie - Konsensuskonferenz St. Gallen 2005 - Anthrazykline - Taxane
--------------------------------------------------------------------------------
Adjuvant chemotherapy for breast cancer
Abstract The efficacy of both adjuvant chemotherapy and hormonal therapy in breast cancer has improved markedly in the past decade. With combined chemo-endocrine therapy, a further improvement in efficacy can be achieved for hormone-receptor positive patients.
Although CMF (cyclophosphamide, methotrexate and fluorouracil) and anthracycline-containing regimens have long been part of the clinical routine in adjuvant chemotherapy, the optimal anthracycline-containing regimens to date appear to be the three agent combinations FEC or FAC given over six cycles (St. Gallen Consensus Conference 2005). Taxane-containing and dose-dense regimens are new chemotherapy concepts that have emerged in the last few years. From large, comparative chemotherapy trials, the efficacy of common chemotherapy regimens can be described as follows: four cycles of adriamycin-cyclophosphamide (AC) is equivalent to six cycles of cyclophosphamide-methotrexate-fluorouracil (CMF) and both are less efficacious than six cycles of fluorouracil-epirubicin/adriamycin-cyclophosphamide (FEC or FAC), which in turn is less efficacious than taxane-containing regimens. A final improvement in efficacy, also over standard taxane-containing regimens, can be achieved with dose-dense regimens. In other words, 4×AC=6×CMF<6×FEC or FACmoderate risk category with highly endocrine responsive tumors) may be adequately treated with hormone therapy alone is ongoing.
This has widespread implications and consequences for therapy costs, therapy duration, and side effect profile or therapeutic index, which must also be considered when deciding on adjuvant therapy. More than ever before, risk-benefit analysis and individualized patient therapy is of the utmost importance.
Keywords Breast cancer - Adjuvant therapy - Consensus Conference St. Gallen 2005 - Anthracyclines - Taxanes
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Chemotherapy-Induced Normalization of FDG Uptake by Colorectal Liver Metastases Does Not Usually Indicate Complete Pathologic Response
Marcus C. B. Tan1, David C. Linehan1, 2, William G. Hawkins1, 2, Barry A. Siegel2, 3 and Steven M. Strasberg1, 2
(1) Section of Hepato–Pancreato–Biliary and GI Surgery, Department of Surgery, Washington University School of Medicine, Suite 1160, Northwest Tower, 660 South Euclid Ave, Box 8109, St. Louis, MO 63110, USA
(2) Alvin J. Siteman Cancer Center, Washington University in Saint Louis, St. Louis, MO 63110, USA
(3) Mallinckrodt Institute of Radiology, Washington University in Saint Louis, St. Louis, MO 63110, USA
Received: 29 May 2007 Accepted: 13 June 2007 Published online: 11 July 2007
Abstract Dramatic responses are being observed in colorectal cancer liver metastases treated with newer chemotherapeutic regimens. These have been associated with normalization of [18F]fluoro-2-deoxy-d-glucose (FDG) uptake (complete metabolic response) on follow-up Positron Emission Tomography with [18F]fluoro-2-deoxy-d-glucose (FDG-PET) scans in some patients. It is unclear how often complete metabolic response is indicative of complete tumor destruction. We analyzed a subset of patients who had neoadjuvant chemotherapy for hepatic metastases from colorectal adenocarcinoma. Inclusion criteria were: (1) FDG-avid hepatic lesions before initiation of chemotherapy; (2) complete metabolic response of the same lesions after chemotherapy; and (3) histopathologic examination of hepatic lesions. Complete pathologic response was defined as no histologically identifiable viable tumor. Fourteen patients fit the inclusion criteria. All had synchronous, hepatic-only colorectal metastases. On microscopic examination, complete pathologic response to the neoadjuvant regimen was found in only 5 of 34 lesions (15%) and in only 3 of the 14 patients (21%). Seven lesions had complete metabolic response and disappeared on computed tomography (CT); of these, six still contained viable tumor. We conclude that complete metabolic response on FDG-PET after neoadjuvant chemotherapy is an unreliable indicator of complete pathologic response. Therefore, currently, curative resection of liver metastases in these patients should not be deferred on the basis of FDG-PET findings.
Keywords Colorectal cancer - Hepatic metastasis - FDG-PET - Response to therapy - Chemotherapy
(1) Section of Hepato–Pancreato–Biliary and GI Surgery, Department of Surgery, Washington University School of Medicine, Suite 1160, Northwest Tower, 660 South Euclid Ave, Box 8109, St. Louis, MO 63110, USA
(2) Alvin J. Siteman Cancer Center, Washington University in Saint Louis, St. Louis, MO 63110, USA
(3) Mallinckrodt Institute of Radiology, Washington University in Saint Louis, St. Louis, MO 63110, USA
Received: 29 May 2007 Accepted: 13 June 2007 Published online: 11 July 2007
Abstract Dramatic responses are being observed in colorectal cancer liver metastases treated with newer chemotherapeutic regimens. These have been associated with normalization of [18F]fluoro-2-deoxy-d-glucose (FDG) uptake (complete metabolic response) on follow-up Positron Emission Tomography with [18F]fluoro-2-deoxy-d-glucose (FDG-PET) scans in some patients. It is unclear how often complete metabolic response is indicative of complete tumor destruction. We analyzed a subset of patients who had neoadjuvant chemotherapy for hepatic metastases from colorectal adenocarcinoma. Inclusion criteria were: (1) FDG-avid hepatic lesions before initiation of chemotherapy; (2) complete metabolic response of the same lesions after chemotherapy; and (3) histopathologic examination of hepatic lesions. Complete pathologic response was defined as no histologically identifiable viable tumor. Fourteen patients fit the inclusion criteria. All had synchronous, hepatic-only colorectal metastases. On microscopic examination, complete pathologic response to the neoadjuvant regimen was found in only 5 of 34 lesions (15%) and in only 3 of the 14 patients (21%). Seven lesions had complete metabolic response and disappeared on computed tomography (CT); of these, six still contained viable tumor. We conclude that complete metabolic response on FDG-PET after neoadjuvant chemotherapy is an unreliable indicator of complete pathologic response. Therefore, currently, curative resection of liver metastases in these patients should not be deferred on the basis of FDG-PET findings.
Keywords Colorectal cancer - Hepatic metastasis - FDG-PET - Response to therapy - Chemotherapy
Chemotherapy-induced nausea and vomiting—incidence and impact on patient quality of life at community oncology settings
Lorenzo Cohen1 , Carl A. de Moor2 , Peter Eisenberg3 , Eileen E. Ming4 and Henry Hu5
(1) Department of Behavioral Science, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA
(2) Children’s Hospital Boston and Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA
(3) California Cancer Care, Suite 200, 1350 South Eliseo Drive, Greenbrae, CA 94904, USA
(4) Discovery Medicine and Epidemiology, AstraZeneca LP, 1800 Concord Pike, FOC-N21-165, Wilmington, DE 19850-5437, USA
(5) Merck & Co., Inc., P.O. Box 4, WP39-130, West Point, PA 19486, USA
Received: 20 June 2006 Accepted: 20 September 2006 Published online: 14 November 2006
Abstract
Goals of work The present study sought to determine the prevalence of acute and delayed chemotherapy-induced nausea and vomiting (CINV) across ten community oncology settings. The effect of CINV on quality of life (QOL) was also evaluated.
Materials and methods Cancer patients who were scheduled for their first cycle of a new chemotherapy regimen were recruited from ten community oncology clinics. Study participants recorded occurrence of CINV by completing a daily diary each day for the first 8 days after treatment during each cycle and the Functional Living Index-Emesis (FLIE) before chemotherapy, at the end of day 1 and day 6 after chemotherapy. Mixed model regression analysis was used to explore the association between occurrence of CINV at cycle 1 and subsequent cycles and its impact on patient QOL.
Main results One hundred and fifty-one patients provided information for at least one cycle. During cycle 1, only 33% had neither acute nor delayed CINV. Of the 36% patients who developed acute CINV, 8% developed acute CINV only. Of the 59% who developed delayed CINV, 53% reported delayed only and 47% reported acute and delayed CINV. A similar pattern was seen at cycles 2 and 3. Experience of CINV at cycle 1 was associated with the development of CINV at cycles 2 and 3. Occurrence of CINV significantly interfered with patient QOL as assessed by the FLIE.
Conclusions CINV remained a substantial problem for patients receiving chemotherapy in this community-based sample, especially delayed CINV. CINV significantly interfered with patient QOL and daily functioning.
Keywords Nausea - Vomiting - Quality of life - Chemotherapy - Cancer
(1) Department of Behavioral Science, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA
(2) Children’s Hospital Boston and Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA
(3) California Cancer Care, Suite 200, 1350 South Eliseo Drive, Greenbrae, CA 94904, USA
(4) Discovery Medicine and Epidemiology, AstraZeneca LP, 1800 Concord Pike, FOC-N21-165, Wilmington, DE 19850-5437, USA
(5) Merck & Co., Inc., P.O. Box 4, WP39-130, West Point, PA 19486, USA
Received: 20 June 2006 Accepted: 20 September 2006 Published online: 14 November 2006
Abstract
Goals of work The present study sought to determine the prevalence of acute and delayed chemotherapy-induced nausea and vomiting (CINV) across ten community oncology settings. The effect of CINV on quality of life (QOL) was also evaluated.
Materials and methods Cancer patients who were scheduled for their first cycle of a new chemotherapy regimen were recruited from ten community oncology clinics. Study participants recorded occurrence of CINV by completing a daily diary each day for the first 8 days after treatment during each cycle and the Functional Living Index-Emesis (FLIE) before chemotherapy, at the end of day 1 and day 6 after chemotherapy. Mixed model regression analysis was used to explore the association between occurrence of CINV at cycle 1 and subsequent cycles and its impact on patient QOL.
Main results One hundred and fifty-one patients provided information for at least one cycle. During cycle 1, only 33% had neither acute nor delayed CINV. Of the 36% patients who developed acute CINV, 8% developed acute CINV only. Of the 59% who developed delayed CINV, 53% reported delayed only and 47% reported acute and delayed CINV. A similar pattern was seen at cycles 2 and 3. Experience of CINV at cycle 1 was associated with the development of CINV at cycles 2 and 3. Occurrence of CINV significantly interfered with patient QOL as assessed by the FLIE.
Conclusions CINV remained a substantial problem for patients receiving chemotherapy in this community-based sample, especially delayed CINV. CINV significantly interfered with patient QOL and daily functioning.
Keywords Nausea - Vomiting - Quality of life - Chemotherapy - Cancer
Adjuvante Chemotherapie bei soliden Tumoren des Gastrointestinaltrakts
G. von Wichert1 und T. Seufferlein1
(1) Klinik für Innere Medizin I, Zentrum für Innere Medizin, Universität Ulm, Robert-Koch-Straße 8, 89081 Ulm
Online publiziert: 28. Oktober 2007
Zusammenfassung Eine chirurgische Therapie strebt die vollständige Entfernung eines Tumors aus dem Organismus an. Eine anschließende adjuvante Chemotherapie soll durch die Beseitigung verbliebener Tumorzellen das Rezidiv verhindern und damit die langfristige Heilung verbessern. In den letzten Jahren konnte durch multimodale Konzepte, unter Einbeziehung neuer Kombinationschemotherapieschemata und innovativer Bestrahlungskonzepte, die langfristige Prognose für den einzelnen Patienten verbessert werden. Ziel dieser Übersicht ist es, die aktuellen Konzepte für ausgewählte Tumore des Gastrointestinaltrakts vorzustellen und zu bewerten.
Schlüsselwörter Adjuvante Chemotherapie - Kolonkarzinom - Pankreaskarzinom - Magenkarzinom
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Adjuvant chemotherapy of solid tumors of the gastrointestinal tract: Where is the progress?
Abstract Surgical therapy of any malignancy always attempts the complete removal of a cancer from the organism. An adjuvant chemotherapy has the goal to remove remaining tumor-cells, to prevent recurrence of the disease and to improve long term survival. Within the last years there has been a substantial improvement in prognosis due to multi-modal therapeutic regimens including combination-chemo-therapy and innovative radiation-protocols. This review aims to present and to critically review current concepts in the treatment of selected tumors of the gastrointestinal tract.
Keywords Adjuvant chemotherapy - Colon cancer - Pancreatic cancer - Gastric cancer
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(1) Klinik für Innere Medizin I, Zentrum für Innere Medizin, Universität Ulm, Robert-Koch-Straße 8, 89081 Ulm
Online publiziert: 28. Oktober 2007
Zusammenfassung Eine chirurgische Therapie strebt die vollständige Entfernung eines Tumors aus dem Organismus an. Eine anschließende adjuvante Chemotherapie soll durch die Beseitigung verbliebener Tumorzellen das Rezidiv verhindern und damit die langfristige Heilung verbessern. In den letzten Jahren konnte durch multimodale Konzepte, unter Einbeziehung neuer Kombinationschemotherapieschemata und innovativer Bestrahlungskonzepte, die langfristige Prognose für den einzelnen Patienten verbessert werden. Ziel dieser Übersicht ist es, die aktuellen Konzepte für ausgewählte Tumore des Gastrointestinaltrakts vorzustellen und zu bewerten.
Schlüsselwörter Adjuvante Chemotherapie - Kolonkarzinom - Pankreaskarzinom - Magenkarzinom
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Adjuvant chemotherapy of solid tumors of the gastrointestinal tract: Where is the progress?
Abstract Surgical therapy of any malignancy always attempts the complete removal of a cancer from the organism. An adjuvant chemotherapy has the goal to remove remaining tumor-cells, to prevent recurrence of the disease and to improve long term survival. Within the last years there has been a substantial improvement in prognosis due to multi-modal therapeutic regimens including combination-chemo-therapy and innovative radiation-protocols. This review aims to present and to critically review current concepts in the treatment of selected tumors of the gastrointestinal tract.
Keywords Adjuvant chemotherapy - Colon cancer - Pancreatic cancer - Gastric cancer
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Chemotherapy-induced nausea and vomiting in routine practice: a European perspective
Agnes Glaus1 , Cornelia Knipping1, Rudolf Morant1, Christel Böhme2, Burkhard Lebert3, Frank Beldermann3, Bernhard Glawogger4, Paz Fernandez Ortega5, André Hüsler6 and Robert Deuson7
(1) Zentrum für Tumordiagnostik und Prävention (ZeTuP), Rorschacher Strasse 150, 9006 St. Gallen, Switzerland
(2) Department of Innere Medizin, Kantonsspital St. Gallen (KSSG), 9007 St. Gallen, Switzerland
(3) Universitätsklinikum Heidelberg Fachweiterbildung, Im Neuenheimer Feld 105, 69120 Heidelberg, Germany
(4) LKH-Universitätsklinikum, Medizinische Universitätsklinik, Auenbruggerplatz 15, 8036 Graz, Austria
(5) Institut Catala Oncologia ICO, Av. Castelldefels s/n/km 2, 7 lHospitalet., 08907 Barcelona, Spain
(6) Institut für mathematische Statistik und Versicherungslehre, Universität Bern, Sidlerstrasse 5, 3012 Bern, Switzerland
(7) Merck & Co., Inc., One Merck Drive, PO Box 100 (WS2E-76), Whitehouse Station, NJ 08889, USA
Received: 7 December 2003 Accepted: 27 May 2004 Published online: 24 July 2004
Abstract
Goals of work The aim of this study was to evaluate the occurrence of chemotherapy-induced nausea and vomiting (CINV) and its effect on patients ability to carry out daily life activities following moderately to highly emetogenic, first-cycle chemotherapy in routine practice in cancer centers of four different European countries.
Patients and methods This was a prospective, cross-sectional, nonrandomized, self-assessment study in 249 patients enrolled from cancer centers in Spain, Austria, Germany, and Switzerland. The study population consisted of 78% women, with a mean age of 54. Breast, lung, and ovarian cancers made up 75% of all cancers in the study. Patients received a mean of 2.0 chemotherapy agents and 2.5 antiemetic drugs.
Main results A total of 450 emetic episodes experienced by 243 patients was recorded over 5 days following chemotherapy, with an average of 1.8 episodes per patient (range: 0–28). A higher percentage of patients (38%) suffered from delayed compared to acute emesis (13%). Between 42% and 52% of all patients suffered from nausea (visual analogue scale 5 mm) on any one day, peaking at day 3. Using the Functional Living Index for Emesis (FLIE) questionnaire, 75% of patients with nausea and 50% with vomiting reported a negative impact of these conditions on performance of daily living.
Conclusions CINV remains a significant problem in routine practice, particularly in the delayed phase posttreatment. Overall, CINV had a negative impact on patients daily life.
Keywords Nausea/emesis - Cancer treatment - Antiemetic therapy - Patient-reported outcomes
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(1) Zentrum für Tumordiagnostik und Prävention (ZeTuP), Rorschacher Strasse 150, 9006 St. Gallen, Switzerland
(2) Department of Innere Medizin, Kantonsspital St. Gallen (KSSG), 9007 St. Gallen, Switzerland
(3) Universitätsklinikum Heidelberg Fachweiterbildung, Im Neuenheimer Feld 105, 69120 Heidelberg, Germany
(4) LKH-Universitätsklinikum, Medizinische Universitätsklinik, Auenbruggerplatz 15, 8036 Graz, Austria
(5) Institut Catala Oncologia ICO, Av. Castelldefels s/n/km 2, 7 lHospitalet., 08907 Barcelona, Spain
(6) Institut für mathematische Statistik und Versicherungslehre, Universität Bern, Sidlerstrasse 5, 3012 Bern, Switzerland
(7) Merck & Co., Inc., One Merck Drive, PO Box 100 (WS2E-76), Whitehouse Station, NJ 08889, USA
Received: 7 December 2003 Accepted: 27 May 2004 Published online: 24 July 2004
Abstract
Goals of work The aim of this study was to evaluate the occurrence of chemotherapy-induced nausea and vomiting (CINV) and its effect on patients ability to carry out daily life activities following moderately to highly emetogenic, first-cycle chemotherapy in routine practice in cancer centers of four different European countries.
Patients and methods This was a prospective, cross-sectional, nonrandomized, self-assessment study in 249 patients enrolled from cancer centers in Spain, Austria, Germany, and Switzerland. The study population consisted of 78% women, with a mean age of 54. Breast, lung, and ovarian cancers made up 75% of all cancers in the study. Patients received a mean of 2.0 chemotherapy agents and 2.5 antiemetic drugs.
Main results A total of 450 emetic episodes experienced by 243 patients was recorded over 5 days following chemotherapy, with an average of 1.8 episodes per patient (range: 0–28). A higher percentage of patients (38%) suffered from delayed compared to acute emesis (13%). Between 42% and 52% of all patients suffered from nausea (visual analogue scale 5 mm) on any one day, peaking at day 3. Using the Functional Living Index for Emesis (FLIE) questionnaire, 75% of patients with nausea and 50% with vomiting reported a negative impact of these conditions on performance of daily living.
Conclusions CINV remains a significant problem in routine practice, particularly in the delayed phase posttreatment. Overall, CINV had a negative impact on patients daily life.
Keywords Nausea/emesis - Cancer treatment - Antiemetic therapy - Patient-reported outcomes
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Adjuvante Behandlungsmöglichkeiten nach operativer Therapie des nichtmetastasierten Nierenzellkarzinoms
C. Doehn1, 2 und D. Jocham1
(1) Klinik und Poliklinik für Urologie, Universitätsklinikum Schleswig-Holstein (UKSH), Campus Lübeck,
(2) Klinik und Poliklinik für Urologie, Universitätsklinikum Schleswig-Holstein (UKSH), Campus Lübeck, Ratzeburger Allee 160, 23538 Lübeck
Online publiziert: 25. August 2004
Zusammenfassung Patienten mit Nierenzellkarzinom haben eine relative Fünfjahresüberlebenswahrscheinlichkeit von 62%. Bei Vorliegen von Metastasen überleben weniger als 10% einen Zeitraum von 5 Jahren. Die Standardtherapie des nichtmetastasierten Nierenzellkarzinoms besteht in einer operativen Entfernung des Tumors. Vor dem Hintergrund der Überlebensdaten ist stadienabhängig die Notwendigkeit einer adjuvanten Behandlung eindeutig. In der Literatur finden sich adjuvante Behandlungsansätze wie die Radiotherapie, die antihormonelle Therapie mittels Medroxyprogesteronazetat, eine Vakzinetherapie mit bestrahlten autologen Tumorzellen oder die Verabreichung von Interferon- oder Interleukin-2. Keiner dieser Therapieansätze konnte einen Vorteil für die behandelten Patienten erbringen. Kürzlich wurden die Ergebnisse einer randomisierten Phase-III-Studie zur Wertigkeit einer adjuvanten Therapie mit einer Tumorzellvakzine (aTL) nach radikaler Nephrektomie publiziert. Für Patienten der Vakzinegruppe zeigte sich eine statistisch signifikante Reduktion des Risikos einer Tumorprogression gegenüber einer Kontrollgruppe ohne adjuvante Therapie.
Schlüsselwörter Nierenzellkarzinom - Adjuvant - Immuntherapie - Zytokine - Vakzine
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Adjuvant treatment options following operative therapy of non-metastatic kidney cancer
Abstract Patients with kidney cancer have a relative 5-year survival of 62%. In the presence of metastases, less than 10% of patients survive 5 years or more. Standard therapy of nonmetastatic kidney cancer is operative tumor removal. Keeping the survival data of kidney cancer in mind, the need for adjuvant therapy is clear. In the literature adjuvant therapeutic strategies such as radiotherapy, antihormonal therapy using medroxyprogesterone acetate, vaccination with irradiated autologous tumor cells, or administration of interferon-alpha or interleukin-2 have been reported. None of these strategies have resulted in an advantage for the study patients. Recently, results from a randomized phase III trial investigating the role of adjuvant therapy with an autologous tumor cell vaccine (aTL) following radical nephrectomy have been published. Patients in the vaccine group demonstrated a statistically significant reduction of the risk of tumor progression compared to patients in the control group without adjuvant therapy.
Keywords Kidney cancer - Adjuvant - Immunotherapy - Cytokine - Vaccine - Autologous
(1) Klinik und Poliklinik für Urologie, Universitätsklinikum Schleswig-Holstein (UKSH), Campus Lübeck,
(2) Klinik und Poliklinik für Urologie, Universitätsklinikum Schleswig-Holstein (UKSH), Campus Lübeck, Ratzeburger Allee 160, 23538 Lübeck
Online publiziert: 25. August 2004
Zusammenfassung Patienten mit Nierenzellkarzinom haben eine relative Fünfjahresüberlebenswahrscheinlichkeit von 62%. Bei Vorliegen von Metastasen überleben weniger als 10% einen Zeitraum von 5 Jahren. Die Standardtherapie des nichtmetastasierten Nierenzellkarzinoms besteht in einer operativen Entfernung des Tumors. Vor dem Hintergrund der Überlebensdaten ist stadienabhängig die Notwendigkeit einer adjuvanten Behandlung eindeutig. In der Literatur finden sich adjuvante Behandlungsansätze wie die Radiotherapie, die antihormonelle Therapie mittels Medroxyprogesteronazetat, eine Vakzinetherapie mit bestrahlten autologen Tumorzellen oder die Verabreichung von Interferon- oder Interleukin-2. Keiner dieser Therapieansätze konnte einen Vorteil für die behandelten Patienten erbringen. Kürzlich wurden die Ergebnisse einer randomisierten Phase-III-Studie zur Wertigkeit einer adjuvanten Therapie mit einer Tumorzellvakzine (aTL) nach radikaler Nephrektomie publiziert. Für Patienten der Vakzinegruppe zeigte sich eine statistisch signifikante Reduktion des Risikos einer Tumorprogression gegenüber einer Kontrollgruppe ohne adjuvante Therapie.
Schlüsselwörter Nierenzellkarzinom - Adjuvant - Immuntherapie - Zytokine - Vakzine
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Adjuvant treatment options following operative therapy of non-metastatic kidney cancer
Abstract Patients with kidney cancer have a relative 5-year survival of 62%. In the presence of metastases, less than 10% of patients survive 5 years or more. Standard therapy of nonmetastatic kidney cancer is operative tumor removal. Keeping the survival data of kidney cancer in mind, the need for adjuvant therapy is clear. In the literature adjuvant therapeutic strategies such as radiotherapy, antihormonal therapy using medroxyprogesterone acetate, vaccination with irradiated autologous tumor cells, or administration of interferon-alpha or interleukin-2 have been reported. None of these strategies have resulted in an advantage for the study patients. Recently, results from a randomized phase III trial investigating the role of adjuvant therapy with an autologous tumor cell vaccine (aTL) following radical nephrectomy have been published. Patients in the vaccine group demonstrated a statistically significant reduction of the risk of tumor progression compared to patients in the control group without adjuvant therapy.
Keywords Kidney cancer - Adjuvant - Immunotherapy - Cytokine - Vaccine - Autologous
Chemotherapy-induced dermatological toxicity: frequencies and impact on quality of life in women’s cancers. Results of a prospective study
Mark Hackbarth1, Norbert Haas1, Christina Fotopoulou1, Werner Lichtenegger1 and Jalid Sehouli1, 2
(1) Department of Gynecology and Obstetrics, Charité, Campus Virchow-Klinikum, University Hospital, Berlin, Germany
(2) Department of Obstetrics and Gynecology, Charité, Campus Virchow-Clinic, Augustenburger Platz 1, 13353 Berlin, Germany
Received: 6 February 2007 Accepted: 11 July 2007 Published online: 7 August 2007
Abstract
Purpose The study aimed to determine the prevalence of dermatological side effects and its impact on quality of life in patients receiving systemic chemotherapy for women’s cancers.
Materials and methods A prospective study was conducted on patients with histologically confirmed advanced women’s cancers who were deemed candidates for adjuvant or palliative chemotherapy. Patients were systemically examined for skin, hair, and nail side effects. The impact of those side effects on their quality of life was assessed using the health-related quality of life score (HRQL).
Results Between April 2001 and October 2001, 91 patients received 1 to 17 (median 4) courses of chemotherapy. Malignancies included breast cancer (n = 39, 43%), ovarian cancer (n = 32, 35%), cervical cancer (n = 12, 13%), endometrial cancer (n = 5, 6%), fallopian tube cancer (n = 2, 2%), and vaginal cancer (n = 1, 1%). Chemotherapy agents included taxanes (n = 42, 46%), PEG doxorubicin (n = 17, 7%), other anthracyclines (epirubicin and doxorubicin; n = 6, 19%), topotecan (n = 13, 14%), and other agents (n = 13, 14%). Overall incidence of skin, nail, and hair side effects was 86.8% (n = 79). Seventeen patients (18.7%) developed a palmo-plantar erythrodysesthesia (PPE), and nine of those (53%) were of grade 3 in common toxicity criteria scale (NCI). Twenty-one patients (23.1%) developed nail changes such as subungual hematomas, onycholysis, and leukonychias or nail loss, while 69 (75.8%) developed hair loss. There was a higher incidence of PPE in patients receiving chemotherapy for palliation rather than cure (percent over percent, p < 0.001, Fisher’s exact test). Using the HRQL score, skin changes were the most frequently reported unpleasant side effect (34.1%), and of those patients who developed PPE, this was reported by n = 8 (47%) as the most unpleasant.
Conclusions Dermatological chemotherapy side effects are frequent after treatment of women’s cancers and have a major impact on quality of life as assessed by HRQL. Counseling of patients with women’s cancers and the profile of side effects of chemotherapeutic agents should be considered before considering an adjuvant or palliative chemotherapy regimen.
Keywords Dermatological side effects - Health-related quality of life - PPE - Alopecia - Chemotherapy - Women’s cancer
(1) Department of Gynecology and Obstetrics, Charité, Campus Virchow-Klinikum, University Hospital, Berlin, Germany
(2) Department of Obstetrics and Gynecology, Charité, Campus Virchow-Clinic, Augustenburger Platz 1, 13353 Berlin, Germany
Received: 6 February 2007 Accepted: 11 July 2007 Published online: 7 August 2007
Abstract
Purpose The study aimed to determine the prevalence of dermatological side effects and its impact on quality of life in patients receiving systemic chemotherapy for women’s cancers.
Materials and methods A prospective study was conducted on patients with histologically confirmed advanced women’s cancers who were deemed candidates for adjuvant or palliative chemotherapy. Patients were systemically examined for skin, hair, and nail side effects. The impact of those side effects on their quality of life was assessed using the health-related quality of life score (HRQL).
Results Between April 2001 and October 2001, 91 patients received 1 to 17 (median 4) courses of chemotherapy. Malignancies included breast cancer (n = 39, 43%), ovarian cancer (n = 32, 35%), cervical cancer (n = 12, 13%), endometrial cancer (n = 5, 6%), fallopian tube cancer (n = 2, 2%), and vaginal cancer (n = 1, 1%). Chemotherapy agents included taxanes (n = 42, 46%), PEG doxorubicin (n = 17, 7%), other anthracyclines (epirubicin and doxorubicin; n = 6, 19%), topotecan (n = 13, 14%), and other agents (n = 13, 14%). Overall incidence of skin, nail, and hair side effects was 86.8% (n = 79). Seventeen patients (18.7%) developed a palmo-plantar erythrodysesthesia (PPE), and nine of those (53%) were of grade 3 in common toxicity criteria scale (NCI). Twenty-one patients (23.1%) developed nail changes such as subungual hematomas, onycholysis, and leukonychias or nail loss, while 69 (75.8%) developed hair loss. There was a higher incidence of PPE in patients receiving chemotherapy for palliation rather than cure (percent over percent, p < 0.001, Fisher’s exact test). Using the HRQL score, skin changes were the most frequently reported unpleasant side effect (34.1%), and of those patients who developed PPE, this was reported by n = 8 (47%) as the most unpleasant.
Conclusions Dermatological chemotherapy side effects are frequent after treatment of women’s cancers and have a major impact on quality of life as assessed by HRQL. Counseling of patients with women’s cancers and the profile of side effects of chemotherapeutic agents should be considered before considering an adjuvant or palliative chemotherapy regimen.
Keywords Dermatological side effects - Health-related quality of life - PPE - Alopecia - Chemotherapy - Women’s cancer
Adjuvant treatment strategies for pancreatic cancer
Erika A. Newman1, Diane M. Simeone1 and Michael W. Mulholland1
(1) From the Section of Gastrointestinal Surgery, Department of Surgery, The University of Michigan Medical Center, Ann Arbor, Michigan
Abstract Pancreatic cancer is a difficult and unsolved surgical problem. It remains one of the top five causes of cancer-related deaths and has the lowest 5-year survival of any cancer, largely due to late diagnosis, low resection rates, and local recurrence. Clinical trials examining the optimal timing and delivery of adjuvant therapies for pancreatic cancer have yielded controversial results. Although most experts agree that the addition of chemotherapy has survival benefit in patients with resectable pancreatic cancer, there is no consensus regarding the optimal therapeutic agents, timing (neoadjuvant versus adjuvant), and the addition of radiation therapy to the treatment regimen. Multiple phase III trials are in progress in efforts to examine these issues. Additionally, exciting progress has been made with novel chemotherapeutic combinations, and alternative treatment modalities including interferon-α, immunotherapy, and pancreatic cancer stem cells. Given the high failure pattern after surgical resection, with more than half of patients developing locoregional recurrence, all patients undergoing pancreaticoduodenectomy are candidates for adjuvant therapy.
Key words Pancreas - pancreatic cancer - adjuvant therapy - neoadjuvant therapy
(1) From the Section of Gastrointestinal Surgery, Department of Surgery, The University of Michigan Medical Center, Ann Arbor, Michigan
Abstract Pancreatic cancer is a difficult and unsolved surgical problem. It remains one of the top five causes of cancer-related deaths and has the lowest 5-year survival of any cancer, largely due to late diagnosis, low resection rates, and local recurrence. Clinical trials examining the optimal timing and delivery of adjuvant therapies for pancreatic cancer have yielded controversial results. Although most experts agree that the addition of chemotherapy has survival benefit in patients with resectable pancreatic cancer, there is no consensus regarding the optimal therapeutic agents, timing (neoadjuvant versus adjuvant), and the addition of radiation therapy to the treatment regimen. Multiple phase III trials are in progress in efforts to examine these issues. Additionally, exciting progress has been made with novel chemotherapeutic combinations, and alternative treatment modalities including interferon-α, immunotherapy, and pancreatic cancer stem cells. Given the high failure pattern after surgical resection, with more than half of patients developing locoregional recurrence, all patients undergoing pancreaticoduodenectomy are candidates for adjuvant therapy.
Key words Pancreas - pancreatic cancer - adjuvant therapy - neoadjuvant therapy
Adjuvant Treatment of Stage II Colon Cancer: Is There a True No-Chemotherapy Group?
Robert C. G. Martin1
(1) Department of Surgery, Division of Surgical Oncology, University of Louisville School of Medicine, 315 East Broadway, Room 313, Louisville, Kentucky, 40202
Received: 29 November 2005 Accepted: 6 December 2005 Published online: 13 April 2006
(1) Department of Surgery, Division of Surgical Oncology, University of Louisville School of Medicine, 315 East Broadway, Room 313, Louisville, Kentucky, 40202
Received: 29 November 2005 Accepted: 6 December 2005 Published online: 13 April 2006
Adjuvant Therapy With Protein-Bound Polysaccharide K and Tegafur Uracil in Patients With Stage II or III Colorectal Cancer: Randomized, Controlled Tri
Susumu Ohwada1 and Susumu Kawate, M.D., Toshiroh Ikeya, M.D., Tadahiro Yokomori, M.D., Teruo Kusaba, M.D., Takashi Roppongi, M.D., Toru Takahashi, M.D., Seiji Nakamura, M.D., Yoshiyuki Kawashima, M.D., Takashi Nakajima, M.D., Yasuo Morishita, M.D.
(1) Gunma Oncology Study Group (GOSG), Maebashi, Gunma, Japan
Abstract PURPOSE: Intravenous fluorouracil and leucovorin for six to eight months is currently a standard adjuvant treatment for Stage III colon cancer; however, this regimen is complex, inconvenient, and has a high intolerability. Adjuvant chemotherapies are claimed for objective response rates with an acceptable safety profile and complexity. We investigated the benefits of oral protein-bound polysaccharide K added to oral tegafur/uracil on curatively resected Stage II or III colorectal cancer. METHODS: We prospectively randomized 207 patients to treatments of either oral 3.0 g protein-bound polysaccharide K plus 300 mg tegafur/uracil or 300 mg tegafur/uracil alone for two years following 12 mg/m2 and 8 mg/m2 mitomycin treatment on postoperative Days 1 and 2, respectively. The primary end points were disease-free and overall survival, and recurrence rates. RESULTS: Three (1.4 percent) patients were declared ineligible, and three patients did not start treatment. In total, 201 patients were analyzed. The three-year, disease-free survival rate was 80.6 percent (standard error = 3.4 percent) in the protein-bound polysaccharide K group (P = 0.02) compared with 68.7 percent (SE = 5.7 percent) in the control group after a median follow-up of 3.7 years. The estimated relative risk of recurrence in the control group was 1.87 (95 percent confidence interval, 1.10–3.20) at three years. The three-year, overall survival rate was 87.3 percent (standard error = 2.9 percent) in the protein-bound polysaccharide K group and 80.6 percent (standard error = 4.8 percent) in the control group (P = 0.24). The three-year, overall survival rate in 80 pathological TNM Stage III patients was 83.0 percent (standard error = 5.2 percent) in the protein-bound polysaccharide K group and 59.3 percent (standard error = 9.5 percent) in the control group (P = 0.02). Protein-bound polysaccharide K prevented distant metastases (P = 0.05), particularly lung metastases (P = 0.01). The incidence of adverse effects was minimal, and compliance was good. CONCLUSION: Adjuvant therapy using a combination of oral protein-bound polysaccharide K and tegafur/uracil is highly effective in preventing the recurrence of colorectal cancer in Stage II or III patients, and increases overall survival in pathological TNM Stage III. These results will be a sufficient proof to conduct a larger study to compare tegafur/uracil/protein-bound polysaccharide K with 5-fluorouracil/ leucovorin.
(1) Gunma Oncology Study Group (GOSG), Maebashi, Gunma, Japan
Abstract PURPOSE: Intravenous fluorouracil and leucovorin for six to eight months is currently a standard adjuvant treatment for Stage III colon cancer; however, this regimen is complex, inconvenient, and has a high intolerability. Adjuvant chemotherapies are claimed for objective response rates with an acceptable safety profile and complexity. We investigated the benefits of oral protein-bound polysaccharide K added to oral tegafur/uracil on curatively resected Stage II or III colorectal cancer. METHODS: We prospectively randomized 207 patients to treatments of either oral 3.0 g protein-bound polysaccharide K plus 300 mg tegafur/uracil or 300 mg tegafur/uracil alone for two years following 12 mg/m2 and 8 mg/m2 mitomycin treatment on postoperative Days 1 and 2, respectively. The primary end points were disease-free and overall survival, and recurrence rates. RESULTS: Three (1.4 percent) patients were declared ineligible, and three patients did not start treatment. In total, 201 patients were analyzed. The three-year, disease-free survival rate was 80.6 percent (standard error = 3.4 percent) in the protein-bound polysaccharide K group (P = 0.02) compared with 68.7 percent (SE = 5.7 percent) in the control group after a median follow-up of 3.7 years. The estimated relative risk of recurrence in the control group was 1.87 (95 percent confidence interval, 1.10–3.20) at three years. The three-year, overall survival rate was 87.3 percent (standard error = 2.9 percent) in the protein-bound polysaccharide K group and 80.6 percent (standard error = 4.8 percent) in the control group (P = 0.24). The three-year, overall survival rate in 80 pathological TNM Stage III patients was 83.0 percent (standard error = 5.2 percent) in the protein-bound polysaccharide K group and 59.3 percent (standard error = 9.5 percent) in the control group (P = 0.02). Protein-bound polysaccharide K prevented distant metastases (P = 0.05), particularly lung metastases (P = 0.01). The incidence of adverse effects was minimal, and compliance was good. CONCLUSION: Adjuvant therapy using a combination of oral protein-bound polysaccharide K and tegafur/uracil is highly effective in preventing the recurrence of colorectal cancer in Stage II or III patients, and increases overall survival in pathological TNM Stage III. These results will be a sufficient proof to conduct a larger study to compare tegafur/uracil/protein-bound polysaccharide K with 5-fluorouracil/ leucovorin.
Chemotherapy versus ovarian ablation as adjuvant therapy for breast cancer: impact on health-related quality of life in a randomized trial
Mogens Groenvold1, 2, 6 , Peter M. Fayers3, 4, Morten Aagaard Petersen1 and Henning T. Mouridsen5
(1) The Research Unit, Department of Palliative Medicine, Bispebjerg Hospital, Copenhagen, Denmark
(2) Department of Health Services Research, Institute of Public Health, University of Copenhagen, Copenhagen, Denmark
(3) Department of Public Health, University of Aberdeen Medical School, Aberdeen, UK
(4) Unit for Applied Clinical Research, Norwegian University of Science and Technology, Trondheim, Norway
(5) Department of Oncology ONK, The Finsen Center, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
(6) The Research Unit, Department of Palliative Medicine, Bispebjerg Hospital, Bispebjerg Bakke 23, DK-2400 Copenhagen, Denmark
Received: 28 December 2005 Accepted: 2 January 2006 Published online: 16 March 2006
Summary
Background Ovarian ablation is an effective adjuvant therapy for primary breast cancer but little is known about its quality of life impact relative to the more widely used adjuvant chemotherapy. This randomized study compared quality of life outcomes of adjuvant ovarian ablation versus cyclophosphamide, methotrexate, fluoracil (CMF) chemotherapy.
Methods The Danish Breast Cancer Cooperative Group (DBCG) trial 89-b randomized premenopausal patients with receptor-positive, primary breast cancer between nine cycles of CMF chemotherapy given every 3 weeks and ovarian ablation by oophorectomy. In total, 317 randomized patients were invited to take part in a longitudinal quality of life study with assessments at 1, 3, 5, 9, 15, and 24 months after randomization. The questionnaire included the EORTC QLQ-C30, the Hospital Anxiety and Depression Scale, and additional items assessing potential symptoms not included in the standard instruments.
Results After 2 years, 260 women were alive and recurrence-free, and 196 of these (75%) had completed all six questionnaires. Overall, patients in the chemotherapy group had more symptomatology at the first three assessments (i.e., during the 6 months treatment period), except for hot flushes/sweats. There were few differences between groups at later assessments. In chemotherapy patients, the likelihood of preserving ovarian function decreased steeply with increasing age. CMF chemotherapy and ovarian ablation have similar impact on recurrence and survival.
Conclusion Chemotherapy had more negative impact on health-related quality of life but preserved ovarian function in some younger patients.
Keywords breast neoplasms - chemotherapy - outcomes - ovarian ablation - quality of life - randomized trial
(1) The Research Unit, Department of Palliative Medicine, Bispebjerg Hospital, Copenhagen, Denmark
(2) Department of Health Services Research, Institute of Public Health, University of Copenhagen, Copenhagen, Denmark
(3) Department of Public Health, University of Aberdeen Medical School, Aberdeen, UK
(4) Unit for Applied Clinical Research, Norwegian University of Science and Technology, Trondheim, Norway
(5) Department of Oncology ONK, The Finsen Center, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
(6) The Research Unit, Department of Palliative Medicine, Bispebjerg Hospital, Bispebjerg Bakke 23, DK-2400 Copenhagen, Denmark
Received: 28 December 2005 Accepted: 2 January 2006 Published online: 16 March 2006
Summary
Background Ovarian ablation is an effective adjuvant therapy for primary breast cancer but little is known about its quality of life impact relative to the more widely used adjuvant chemotherapy. This randomized study compared quality of life outcomes of adjuvant ovarian ablation versus cyclophosphamide, methotrexate, fluoracil (CMF) chemotherapy.
Methods The Danish Breast Cancer Cooperative Group (DBCG) trial 89-b randomized premenopausal patients with receptor-positive, primary breast cancer between nine cycles of CMF chemotherapy given every 3 weeks and ovarian ablation by oophorectomy. In total, 317 randomized patients were invited to take part in a longitudinal quality of life study with assessments at 1, 3, 5, 9, 15, and 24 months after randomization. The questionnaire included the EORTC QLQ-C30, the Hospital Anxiety and Depression Scale, and additional items assessing potential symptoms not included in the standard instruments.
Results After 2 years, 260 women were alive and recurrence-free, and 196 of these (75%) had completed all six questionnaires. Overall, patients in the chemotherapy group had more symptomatology at the first three assessments (i.e., during the 6 months treatment period), except for hot flushes/sweats. There were few differences between groups at later assessments. In chemotherapy patients, the likelihood of preserving ovarian function decreased steeply with increasing age. CMF chemotherapy and ovarian ablation have similar impact on recurrence and survival.
Conclusion Chemotherapy had more negative impact on health-related quality of life but preserved ovarian function in some younger patients.
Keywords breast neoplasms - chemotherapy - outcomes - ovarian ablation - quality of life - randomized trial
Adjuvant therapy trials of radiotherapy and systemic treatment for breast cancer
Betty A. Mincey1, Laura A. Vallow1 and Edith A. Perez1
(1) Division of Hematology/Oncology, Mayo Clinic and Foundation, 4500 San Pablo Road, 32224 Jacksonville, FL, USA
(1) Division of Hematology/Oncology, Mayo Clinic and Foundation, 4500 San Pablo Road, 32224 Jacksonville, FL, USA
Chemotherapy through mitochondrial apoptosis using nutritional supplements and herbs: A brief overview
Kang-Beom Kwon1, Byung-Hyun Park2 and Do-Gon Ryu1
(1) Department of Physiology, School of Oriental Medicine, Wonkwang University, Iksan, 570-749, Jeonbuk, Korea
(2) Department of Biochemistry, Medical School, and Institute for Healthcare Technology Development, Chonbuk National University, Jeonju, 561-756, Jeonbuk, Korea
Published online: 16 February 2007
Abstract There has been increased interest in the use of naturally occurring compounds with chemopreventive and chemotherapeutic effects in the treatment of cancers. This review summarizes the most recent advances that provide new insights into the molecular mechanisms underlying the apoptotic potential of nutritional supplements and herbs. Apoptosis is an essential process in the pathogenesis of cancer and its mechanisms can be subdivided into either a death receptor-dependent extrinsic pathway or an independent (mitochondrial or intrinsic) pathway. Nutritional supplements and herbs can exert their effects on such pathways separately, sequentially, or in a manner of “crosstalk” between pathways. A strong correlation between the early collapse of the mitochondrial membrane potential and apoptosis was found for most nutritional supplements and herbs that have been studied. These observations provide examples of the development of mitochondrial targeting strategies for cancer therapy.
Keywords Mitochondria - Apoptosis - Herb - Nutritional supplement
(1) Department of Physiology, School of Oriental Medicine, Wonkwang University, Iksan, 570-749, Jeonbuk, Korea
(2) Department of Biochemistry, Medical School, and Institute for Healthcare Technology Development, Chonbuk National University, Jeonju, 561-756, Jeonbuk, Korea
Published online: 16 February 2007
Abstract There has been increased interest in the use of naturally occurring compounds with chemopreventive and chemotherapeutic effects in the treatment of cancers. This review summarizes the most recent advances that provide new insights into the molecular mechanisms underlying the apoptotic potential of nutritional supplements and herbs. Apoptosis is an essential process in the pathogenesis of cancer and its mechanisms can be subdivided into either a death receptor-dependent extrinsic pathway or an independent (mitochondrial or intrinsic) pathway. Nutritional supplements and herbs can exert their effects on such pathways separately, sequentially, or in a manner of “crosstalk” between pathways. A strong correlation between the early collapse of the mitochondrial membrane potential and apoptosis was found for most nutritional supplements and herbs that have been studied. These observations provide examples of the development of mitochondrial targeting strategies for cancer therapy.
Keywords Mitochondria - Apoptosis - Herb - Nutritional supplement
Chemotherapy sensitivity and resistance testing: to be “standard” or to be individualized, that is the question
Tetsuro Kubota1 and Larry Weisenthal2
(1) Center for Advanced and Comprehensive Medicine, Keio University Hospital, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan
(2) Weisenthal Cancer Group, Huntington Beach, CA, USA
Received: 16 January 2006 Accepted: 08 February 2006
Abstract Radical surgery with extended lymph-node dissection is the treatment of first choice and the only curative treatment for locally advanced gastric cancer. While recent combination chemotherapy with S-1 (a combination of tegafur with two biomodulators, gimeracil and oteracil) has achieved high response rates, controversy still remains regarding the significance of adjuvant cancer chemotherapy after surgery. We have been applying chemosensitivity testing in evaluating the appropriate adjuvant cancer chemotherapy for advanced gastric cancer. Our multiple studies have indicated that this chemosensitivity testing would be useful to improve the results of adjuvant chemotherapy, by increasing survivals in the sensitive group. The chemosensitivity testing is approved as “advanced clinical medicine” by the Japanese Ministry of Health, Welfare, and Labor at 11 institutes at present. While complete lymph-node dissection and chemosensitivity test-guided adjuvant chemotherapy has been reported to result in a survival benefit for patients with advanced gastrointestinal cancer, the clinical utility of the testing should be established by means of prospective, randomized clinical trials. Two pivotal clinical trials have been initiated to clarify the utility of chemosensitivity testing in the selection of the appropriate adjuvant cancer chemotherapy for gastric cancer.
Key words Chemosensitivity testing - MTT assay - Histoculture drug-response assay - Gastric cancer - Clinical trial
(1) Center for Advanced and Comprehensive Medicine, Keio University Hospital, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan
(2) Weisenthal Cancer Group, Huntington Beach, CA, USA
Received: 16 January 2006 Accepted: 08 February 2006
Abstract Radical surgery with extended lymph-node dissection is the treatment of first choice and the only curative treatment for locally advanced gastric cancer. While recent combination chemotherapy with S-1 (a combination of tegafur with two biomodulators, gimeracil and oteracil) has achieved high response rates, controversy still remains regarding the significance of adjuvant cancer chemotherapy after surgery. We have been applying chemosensitivity testing in evaluating the appropriate adjuvant cancer chemotherapy for advanced gastric cancer. Our multiple studies have indicated that this chemosensitivity testing would be useful to improve the results of adjuvant chemotherapy, by increasing survivals in the sensitive group. The chemosensitivity testing is approved as “advanced clinical medicine” by the Japanese Ministry of Health, Welfare, and Labor at 11 institutes at present. While complete lymph-node dissection and chemosensitivity test-guided adjuvant chemotherapy has been reported to result in a survival benefit for patients with advanced gastrointestinal cancer, the clinical utility of the testing should be established by means of prospective, randomized clinical trials. Two pivotal clinical trials have been initiated to clarify the utility of chemosensitivity testing in the selection of the appropriate adjuvant cancer chemotherapy for gastric cancer.
Key words Chemosensitivity testing - MTT assay - Histoculture drug-response assay - Gastric cancer - Clinical trial
Adjuvant therapy of colon cancer in idiopathic leukopenia
Hassan Pervez1 , Anil Potti2 and Syed A. Mehdi3
(1) Department of Internal Medicine, University of North Dakota School of Medicine and Health Sciences, MeritCare Hospital [RT 170], 58122 Fargo, ND
(2) Department of Internal Medicine, University of North Dakota School of Medicine and Health Sciences, 1919 Elm St. N, 58102 Fargo, ND
(3) VA Medical Center, 2101 Elm St. N, 58102 Fargo, ND
Received: 22 November 2002 Accepted: 12 December 2002
Abstract Colorectal cancer is a common malignancy. Surgical resection is the primary treatment modality and the outcome is closely related to the extent of the disease at presentation. Adjuvant chemotherapy with 5-fluorouracil and leucovorin is the standard therapy for resected node-positive disease. This therapy can cause myelosuppression. We present a case of colon cancer with idiopathic leukopenia who tolerated chemotherapy without worsening of leukopenia.
Key Words Colon cancer - leukopenia - chemotherapy
(1) Department of Internal Medicine, University of North Dakota School of Medicine and Health Sciences, MeritCare Hospital [RT 170], 58122 Fargo, ND
(2) Department of Internal Medicine, University of North Dakota School of Medicine and Health Sciences, 1919 Elm St. N, 58102 Fargo, ND
(3) VA Medical Center, 2101 Elm St. N, 58102 Fargo, ND
Received: 22 November 2002 Accepted: 12 December 2002
Abstract Colorectal cancer is a common malignancy. Surgical resection is the primary treatment modality and the outcome is closely related to the extent of the disease at presentation. Adjuvant chemotherapy with 5-fluorouracil and leucovorin is the standard therapy for resected node-positive disease. This therapy can cause myelosuppression. We present a case of colon cancer with idiopathic leukopenia who tolerated chemotherapy without worsening of leukopenia.
Key Words Colon cancer - leukopenia - chemotherapy
Adjuvant therapy in completely resected non-small-cell lung cancer
Giorgio V. Scagliotti1 and Silvia Novello1
(1) Department of Clinical and Biological Sciences, University of Turin, S. Luigi Hospital, Thoracic Oncology Unit, Regione Gonzole, 10, 10043 Orbassano, Torino, Italy
Abstract Less than 20% to 25% of patients with non-small-cell lung cancer (NSCLC) present with stage I or II disease and are best treated by surgical resection. Long-term survival in early NSCLC remains poor. The 5-year survival rate of patients who undergo complete surgical resection is only 40% to 50%. The majority of relapses after surgery are distant metastases; the risk of a local recurrence after complete resection is less than 10%. Postoperative treatments, including chemotherapy, radiotherapy, or both modalities together, have been evaluated widely, but unfortunately none of these treatments have demonstrated any significant impact on survival. Data regarding large-scale adjuvant chemotherapy trials that were closed for accrual almost 4 to 5 years ago will be fully available before the end of the year. It is hoped that a specific meta-analysis will be performed on the basis of these data.
(1) Department of Clinical and Biological Sciences, University of Turin, S. Luigi Hospital, Thoracic Oncology Unit, Regione Gonzole, 10, 10043 Orbassano, Torino, Italy
Abstract Less than 20% to 25% of patients with non-small-cell lung cancer (NSCLC) present with stage I or II disease and are best treated by surgical resection. Long-term survival in early NSCLC remains poor. The 5-year survival rate of patients who undergo complete surgical resection is only 40% to 50%. The majority of relapses after surgery are distant metastases; the risk of a local recurrence after complete resection is less than 10%. Postoperative treatments, including chemotherapy, radiotherapy, or both modalities together, have been evaluated widely, but unfortunately none of these treatments have demonstrated any significant impact on survival. Data regarding large-scale adjuvant chemotherapy trials that were closed for accrual almost 4 to 5 years ago will be fully available before the end of the year. It is hoped that a specific meta-analysis will be performed on the basis of these data.
Adjuvant therapy for stage II colorectal cancer: Who and with what?
Ki-Young Y. Chung1 and David Kelsen
(1) Gastrointestinal Oncology Service, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, 10021 New York, NY, USA
Opinion statement The role of adjuvant chemotherapy for patients with stage II colon adenocarcinoma remains controversial. The high surgical cure rate for patients with "low-riskrd stage II colon cancer, ranging from 75% to 80%, and the available clinical trials and metaanalyses provide conflicting recommendations for or against adjuvant chemotherapy for this group of patients. For fit "high-riskrd stage II patients with clinical obstruction or perforation at presentation, in which the 5-year survival rate is 60% to 70%, there is little controversy, as these patients are routinely treated with adjuvant chemotherapy. Other potential high-risk factors, including high histologic grade, microsatellite instability, and loss of 18q, have yet to be validated in prospective trials. Patients with fewer than 12 regional lymph nodes identified in the surgical specimen have a statistically unclear risk of lymph node involvement. These patients may have stage III disease and should receive adjuvant therapy. The decision to use adjuvant chemotherapy to treat low-risk stage II colon cancer patients (no obstruction or perforation) should be an informed decision weighing the magnitude of a net 2% to 5% survival benefit, a 0.5% to 1.0% risk of mortality with chemotherapy in addition to 6 months of chemotherapy-related toxicities, other coexisting patient morbidities, and the anticipated life expectancy of each patient. As adjuvant chemotherapy is therapy addressing local or metastatic microscopic disease, and the effectiveness of systemic and biologically targeted therapy for advanced macroscopic colon cancer continues to improve rapidly, it remains to be determined by clinical trials whether therapies including newer agents such as cetuximab and bevacizumab administered in the adjuvant setting may affect survival for stage II cancer patients.
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(1) Gastrointestinal Oncology Service, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, 10021 New York, NY, USA
Opinion statement The role of adjuvant chemotherapy for patients with stage II colon adenocarcinoma remains controversial. The high surgical cure rate for patients with "low-riskrd stage II colon cancer, ranging from 75% to 80%, and the available clinical trials and metaanalyses provide conflicting recommendations for or against adjuvant chemotherapy for this group of patients. For fit "high-riskrd stage II patients with clinical obstruction or perforation at presentation, in which the 5-year survival rate is 60% to 70%, there is little controversy, as these patients are routinely treated with adjuvant chemotherapy. Other potential high-risk factors, including high histologic grade, microsatellite instability, and loss of 18q, have yet to be validated in prospective trials. Patients with fewer than 12 regional lymph nodes identified in the surgical specimen have a statistically unclear risk of lymph node involvement. These patients may have stage III disease and should receive adjuvant therapy. The decision to use adjuvant chemotherapy to treat low-risk stage II colon cancer patients (no obstruction or perforation) should be an informed decision weighing the magnitude of a net 2% to 5% survival benefit, a 0.5% to 1.0% risk of mortality with chemotherapy in addition to 6 months of chemotherapy-related toxicities, other coexisting patient morbidities, and the anticipated life expectancy of each patient. As adjuvant chemotherapy is therapy addressing local or metastatic microscopic disease, and the effectiveness of systemic and biologically targeted therapy for advanced macroscopic colon cancer continues to improve rapidly, it remains to be determined by clinical trials whether therapies including newer agents such as cetuximab and bevacizumab administered in the adjuvant setting may affect survival for stage II cancer patients.
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Adjuvant therapy for resected non-small-cell lung cancer: Recent advances, emerging agents, and lingering questions
Tara L. Lin1 and Julie R. Brahmer1
(1) The Bunting-Blaustein Cancer Research Building, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, 1650 Orleans Street, Room G-94, 21231-1000 Baltimore, MD, USA
Abstract Survival rates for all stages of non-small-cell lung cancer (NSCLC) are dismal. Despite complete resection of earlystage NSCLC, many patients have recurrence at distant metastatic sites, reinforcing the need for effective systemic adjuvant therapy. Chemotherapy, and more recently, targeted therapies, have been evaluated in the adjuvant setting. Although initial trials did not suggest improved survival, a 1995 meta-analysis favored adjuvant cisplatin-based chemotherapy. The recently published International Adjuvant Lung Trial confirms this finding and suggests a new standard of care. In this paper we review data on adjuvant chemotherapy and limitations of recent clinical trials, including those with targeted therapies. We also address the most effective and least toxic regimens for adjuvant chemotherapy and the subsets of patients likely to derive the most benefit.
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(1) The Bunting-Blaustein Cancer Research Building, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, 1650 Orleans Street, Room G-94, 21231-1000 Baltimore, MD, USA
Abstract Survival rates for all stages of non-small-cell lung cancer (NSCLC) are dismal. Despite complete resection of earlystage NSCLC, many patients have recurrence at distant metastatic sites, reinforcing the need for effective systemic adjuvant therapy. Chemotherapy, and more recently, targeted therapies, have been evaluated in the adjuvant setting. Although initial trials did not suggest improved survival, a 1995 meta-analysis favored adjuvant cisplatin-based chemotherapy. The recently published International Adjuvant Lung Trial confirms this finding and suggests a new standard of care. In this paper we review data on adjuvant chemotherapy and limitations of recent clinical trials, including those with targeted therapies. We also address the most effective and least toxic regimens for adjuvant chemotherapy and the subsets of patients likely to derive the most benefit.
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Chemotherapy plus bevacizumab in the first-line treatment of non-small cell lung cancer: benefits, risks and limitations
F. Grossi1 , A. Brianti1, C. Defferrari1 and P. Pronzato1
(1) Medical Oncology A, Disease Management Team – Lung Cancer, National Institute for Cancer Research, Genova, Italy
Received: 10 December 2007 Accepted: 16 December 2007
Summary Though chemotherapy remains a mainstay of non-small cell lung cancer (NSCLC) treatment, its efficacy has probably reached a plateau. The management of advanced NSCLC has evolved considerably in recent years due to a progressive understanding of tumour biology and the identification of promising molecular targets. Bevacizumab is a monoclonal antibody targeting vascular endothelial growth factor (VEGF), a key signalling protein in tumour neoangiogenesis, growth and dissemination. The finding in study E4599 of a survival benefit for carboplatin-paclitaxel plus bevacizumab over chemotherapy alone led the U.S. FDA to approve the novel combination for the first-line treatment of patients with advanced, non-squamous NSCLC. This study is the first to show a survival advantage with the addition of a targeted agent to chemotherapy in this setting: in particular, for the first time the survival of NSCLC patients has been extended beyond one year. Recently, in a randomised phase III trial, patients receiving cisplatin-gemcitabine plus bevacizumab experienced a significantly longer progression-free survival compared to the standard arm. Based on these data, the EMEA has just issued a positive opinion to extend the drug's indication to include first-line treatment – in combination with any platinum-based chemotherapy – of advanced, non-squamous NSCLC. The aim of this review is to provide an overview of the evidence supporting the emergence of this new treatment. Key questions – including the optimal dose of bevacizumab, safety of the drug in special populations, the selection of patients most likely to benefit from the treatment, the role of maintenance – are addressed.
Keywords Advanced non-small cell lung cancer - Angiogenesis - Bevacizumab - Chemotherapy - Targeted therapies
(1) Medical Oncology A, Disease Management Team – Lung Cancer, National Institute for Cancer Research, Genova, Italy
Received: 10 December 2007 Accepted: 16 December 2007
Summary Though chemotherapy remains a mainstay of non-small cell lung cancer (NSCLC) treatment, its efficacy has probably reached a plateau. The management of advanced NSCLC has evolved considerably in recent years due to a progressive understanding of tumour biology and the identification of promising molecular targets. Bevacizumab is a monoclonal antibody targeting vascular endothelial growth factor (VEGF), a key signalling protein in tumour neoangiogenesis, growth and dissemination. The finding in study E4599 of a survival benefit for carboplatin-paclitaxel plus bevacizumab over chemotherapy alone led the U.S. FDA to approve the novel combination for the first-line treatment of patients with advanced, non-squamous NSCLC. This study is the first to show a survival advantage with the addition of a targeted agent to chemotherapy in this setting: in particular, for the first time the survival of NSCLC patients has been extended beyond one year. Recently, in a randomised phase III trial, patients receiving cisplatin-gemcitabine plus bevacizumab experienced a significantly longer progression-free survival compared to the standard arm. Based on these data, the EMEA has just issued a positive opinion to extend the drug's indication to include first-line treatment – in combination with any platinum-based chemotherapy – of advanced, non-squamous NSCLC. The aim of this review is to provide an overview of the evidence supporting the emergence of this new treatment. Key questions – including the optimal dose of bevacizumab, safety of the drug in special populations, the selection of patients most likely to benefit from the treatment, the role of maintenance – are addressed.
Keywords Advanced non-small cell lung cancer - Angiogenesis - Bevacizumab - Chemotherapy - Targeted therapies
Adjuvant therapy for resected non-small-cell lung cancer: Past, present, and future
Rosalyn A. Juergens1 and Julie R. Brahmer1
(1) The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, 410 North Broadway, 21231-2410 Baltimore, MD, USA
Abstract Non-small-cell lung cancer has the highest mortality of all malignancies worldwide. Unfortunately, only the minority of patients diagnosed will have potentially curable disease. Over the past 30 years, dozens of trials have been conducted assessing adjuvant treatments to augment the survival advantage offered by surgery. It has only been in the past 5 years that promising results have begun to be seen. Cisplatin-based therapy has now been shown to provide an additional survival benefit in several trials and in a recent meta-analysis. The goal of this paper is to review the data on adjuvant therapies that have emerged over the past 30 years, focusing specifically on the trials that have been published in the past 5 years.
(1) The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, 410 North Broadway, 21231-2410 Baltimore, MD, USA
Abstract Non-small-cell lung cancer has the highest mortality of all malignancies worldwide. Unfortunately, only the minority of patients diagnosed will have potentially curable disease. Over the past 30 years, dozens of trials have been conducted assessing adjuvant treatments to augment the survival advantage offered by surgery. It has only been in the past 5 years that promising results have begun to be seen. Cisplatin-based therapy has now been shown to provide an additional survival benefit in several trials and in a recent meta-analysis. The goal of this paper is to review the data on adjuvant therapies that have emerged over the past 30 years, focusing specifically on the trials that have been published in the past 5 years.
Adjuvant therapy for resectable liver metastases: Can metastatic colorectal cancer be cured?
Vikas Aurora and Mary F. Mulcahy1
(1) Northwestern University, 676 North Saint Clair, Suite 850, Chicago, IL 60611, USA
Published online: 8 July 2007
Abstract Surgery remains the only curative therapy for patients with liver metastases from colorectal cancer. Unfortunately, only a minority of patients are candidates. The use of clinical prognostic indicators and computer programs, such as OncoSurge, may help to identify optimal candidates. Neoadjuvant chemotherapy may render previously ineligible patient candidates for curative surgery after downsizing. Neoadjuvant chemotherapy is associated with histopathologic changes of the liver, and the effect of such changes on survival is unclear. Promising results have been seen with chemotherapy infused through the hepatic artery in conjunction with systemic chemotherapy in the neoadjuvant and adjuvant settings. Adjuvant therapy with oxaliplatin-or irinotecan-based regimens after resection of liver metastases is generally recommended. Individuals should be encouraged to participate in clinical trials to help clarify the role and optimal sequencing of systemic chemotherapy, targeted agents, local therapies, and surgery for patients with hepatic metastases from colorectal cancer.
(1) Northwestern University, 676 North Saint Clair, Suite 850, Chicago, IL 60611, USA
Published online: 8 July 2007
Abstract Surgery remains the only curative therapy for patients with liver metastases from colorectal cancer. Unfortunately, only a minority of patients are candidates. The use of clinical prognostic indicators and computer programs, such as OncoSurge, may help to identify optimal candidates. Neoadjuvant chemotherapy may render previously ineligible patient candidates for curative surgery after downsizing. Neoadjuvant chemotherapy is associated with histopathologic changes of the liver, and the effect of such changes on survival is unclear. Promising results have been seen with chemotherapy infused through the hepatic artery in conjunction with systemic chemotherapy in the neoadjuvant and adjuvant settings. Adjuvant therapy with oxaliplatin-or irinotecan-based regimens after resection of liver metastases is generally recommended. Individuals should be encouraged to participate in clinical trials to help clarify the role and optimal sequencing of systemic chemotherapy, targeted agents, local therapies, and surgery for patients with hepatic metastases from colorectal cancer.
Adjuvant therapy for gastric cancer: A reality at last
J. Randolph Hecht1
(1) Division of Hematology/Oncology, UCLA School of Medicine, 2345H PVUB, 10945 LeConte Avenue, 90095 Los Angeles, CA, USA
Abstract Gastric cancer remains a significant healthcare problem throughout the world and is usually diagnosed at a fairly advanced stage in the West. Despite complete resection of the primary tumor, most patients eventually experience a relapse and die of recurrent disease. Extended surgery has not been shown to improve survival in Western studies. There have been a large number of adjuvant chemotherapy trials over the past several decades, most with negative results. More recently, there is hope for improving these dismal results with a meta-analysis showing a benefit for adjuvant chemotherapy and a large randomized trial, INT-0116, which has just reported a significant survival advantage with combined chemoradiation. These results make adjuvant therapy for completely resected gastric carcinoma the new standard of care, except in the uncommon setting of early intramucosal cancers.
(1) Division of Hematology/Oncology, UCLA School of Medicine, 2345H PVUB, 10945 LeConte Avenue, 90095 Los Angeles, CA, USA
Abstract Gastric cancer remains a significant healthcare problem throughout the world and is usually diagnosed at a fairly advanced stage in the West. Despite complete resection of the primary tumor, most patients eventually experience a relapse and die of recurrent disease. Extended surgery has not been shown to improve survival in Western studies. There have been a large number of adjuvant chemotherapy trials over the past several decades, most with negative results. More recently, there is hope for improving these dismal results with a meta-analysis showing a benefit for adjuvant chemotherapy and a large randomized trial, INT-0116, which has just reported a significant survival advantage with combined chemoradiation. These results make adjuvant therapy for completely resected gastric carcinoma the new standard of care, except in the uncommon setting of early intramucosal cancers.
Adjuvant therapy for colon cancer based on pharmacogenomics?
Erick Gamelin1 , Michele Boisdron-Celle, Alain Morel, Olivier Capitain and Olivier Coqueret
(1) Oncopharmacology-Pharmacogenetics Laboratory, INSERM U, Anticancer Center Paul Papin, 2 rue Moll, 49933 Angers Cedex 9, France
Published online: 8 July 2007
Abstract The impact of adjuvant chemotherapy for patients with localized colon adenocarcinoma is obvious for stage III and high-risk stage II patients but remains somewhat controversial for low-risk stage II. Until now, the decision of an adjuvant chemotherapy is based on pathologic and clinical data. However, some important questions remain. In stage III, how can we improve the results? In low-risk stage II patients, who will benefit from adjuvant chemotherapy? In the event that an adjuvant therapy is decided, which drugs will be chosen, and is the patient at high risk of toxicity because of metabolic deficiency? Different approaches have been developed: 1) genetics to detect DNA mutations or variants in the primary tumor or the patient himself, 2) RNA expression quantification either based on microarray or with real-time quantitative reverse transcriptase-polymerase chain reaction, and 3) protein expression by immunohistochemistry. Despite promising results from retrospective or prospective studies, the available data remain insufficient to draw guidelines. Genetics with the detection of microsatellite instability status and loss of heterozygoty is investigated for validation in large international prospective ongoing clinical trials. Some genes, such as excision repair cross complementing 1, thymidylate synthase, mismatch repair seem to be very good candidates to predict sensitivity to certain drugs. Clearly, the major potential interest of biologic markers highlights the need of multicentric prospective clinical trials to answer crucial questions about adjuvant therapy.
(1) Oncopharmacology-Pharmacogenetics Laboratory, INSERM U, Anticancer Center Paul Papin, 2 rue Moll, 49933 Angers Cedex 9, France
Published online: 8 July 2007
Abstract The impact of adjuvant chemotherapy for patients with localized colon adenocarcinoma is obvious for stage III and high-risk stage II patients but remains somewhat controversial for low-risk stage II. Until now, the decision of an adjuvant chemotherapy is based on pathologic and clinical data. However, some important questions remain. In stage III, how can we improve the results? In low-risk stage II patients, who will benefit from adjuvant chemotherapy? In the event that an adjuvant therapy is decided, which drugs will be chosen, and is the patient at high risk of toxicity because of metabolic deficiency? Different approaches have been developed: 1) genetics to detect DNA mutations or variants in the primary tumor or the patient himself, 2) RNA expression quantification either based on microarray or with real-time quantitative reverse transcriptase-polymerase chain reaction, and 3) protein expression by immunohistochemistry. Despite promising results from retrospective or prospective studies, the available data remain insufficient to draw guidelines. Genetics with the detection of microsatellite instability status and loss of heterozygoty is investigated for validation in large international prospective ongoing clinical trials. Some genes, such as excision repair cross complementing 1, thymidylate synthase, mismatch repair seem to be very good candidates to predict sensitivity to certain drugs. Clearly, the major potential interest of biologic markers highlights the need of multicentric prospective clinical trials to answer crucial questions about adjuvant therapy.
Adjuvant therapy for Colon Cancer
Olivia Aranha and Al B. Benson1
(1) Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Division of Hematology/Oncology, 676 N. St. Clair, Suite 850, Chicago, IL 60611, USA
Published online: 3 October 2007
Abstract In patients with colon cancer who undergo resection for potential cure, 40% to 60% have advanced locoregional disease and are classified as either stage II or stage III. The role of adjuvant therapy in stage III colon cancer is well defined. The results from the MOSAIC trial (Multicenter International Study of Oxaliplatin/5-Fluorouracil/Leucovorin in the Adjuvant Treatment of Colon Cancer) and the National Surgical Adjuvant Breast and Bowel Project C-07 trial confirm a definite disease-free survival (DFS) benefit with the addition of oxaliplatin to either infusional or bolus 5-fluorouracil/leucovorin (5-FU/LV). The Xeloda in Adjuvant Colon Cancer Therapy (X-ACT) trial showed capecitabine to be of equivalent clinical benefit to bolus 5-FU/LV. However, adjuvant trials with irinotecan, including Cancer and Leukemia Group B (CALGB 89803), the Pan-European Trial in Adjuvant Colorectal Cancer 3 (PETACC-3), and the French ACCORD trial, have not shown a significant DFS advantage. In contrast, in patients with stage II disease, a small survival benefit of 1% to 5% exists with chemotherapy. Perhaps the analysis of molecular markers in combination with high-risk histopathologic features will help increase patient specificity and identify subsets of patients with stage II colon cancer who will derive a survival benefit with adjuvant therapy. The current Intergroup study stratifying stage II patients based on presence of microsatellite instability and loss of heterozygosity 18q allele will help us better understand the risk versus benefit observed.
(1) Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Division of Hematology/Oncology, 676 N. St. Clair, Suite 850, Chicago, IL 60611, USA
Published online: 3 October 2007
Abstract In patients with colon cancer who undergo resection for potential cure, 40% to 60% have advanced locoregional disease and are classified as either stage II or stage III. The role of adjuvant therapy in stage III colon cancer is well defined. The results from the MOSAIC trial (Multicenter International Study of Oxaliplatin/5-Fluorouracil/Leucovorin in the Adjuvant Treatment of Colon Cancer) and the National Surgical Adjuvant Breast and Bowel Project C-07 trial confirm a definite disease-free survival (DFS) benefit with the addition of oxaliplatin to either infusional or bolus 5-fluorouracil/leucovorin (5-FU/LV). The Xeloda in Adjuvant Colon Cancer Therapy (X-ACT) trial showed capecitabine to be of equivalent clinical benefit to bolus 5-FU/LV. However, adjuvant trials with irinotecan, including Cancer and Leukemia Group B (CALGB 89803), the Pan-European Trial in Adjuvant Colorectal Cancer 3 (PETACC-3), and the French ACCORD trial, have not shown a significant DFS advantage. In contrast, in patients with stage II disease, a small survival benefit of 1% to 5% exists with chemotherapy. Perhaps the analysis of molecular markers in combination with high-risk histopathologic features will help increase patient specificity and identify subsets of patients with stage II colon cancer who will derive a survival benefit with adjuvant therapy. The current Intergroup study stratifying stage II patients based on presence of microsatellite instability and loss of heterozygosity 18q allele will help us better understand the risk versus benefit observed.
Chemotherapy of prostate cancer: Present and future Donald Trump1 and Yiu-Keung Lau1
Donald Trump1 and Yiu-Keung Lau1
(1) Department of Medicine, Roswell Park Cancer Institute, Elm and Carlton Streets, 14263 Buffalo, NY, USA
Abstract The role of chemotherapy in prostate cancer continues to evolve. In men with symptomatic androgen-independent prostate cancer, significant reduction in pain and analgesic requirements are achievable with mitoxantrone and glucocorticoid combinations compared with glucocorticoids alone. However, survival rates are not improved. Taxane-based combinations with estramustine phosphate or other new agents show promise. Prostate-specific antigen response rates with these combinations appear to be 1.5 to 2 times more frequent than with mitoxantrone-based combinations. Randomized trials of taxane versus mitoxantrone-based therapies are underway. New agents and applications of current agents in adjuvant settings should be explored if survival in men with prostate cancer is to be improved.
(1) Department of Medicine, Roswell Park Cancer Institute, Elm and Carlton Streets, 14263 Buffalo, NY, USA
Abstract The role of chemotherapy in prostate cancer continues to evolve. In men with symptomatic androgen-independent prostate cancer, significant reduction in pain and analgesic requirements are achievable with mitoxantrone and glucocorticoid combinations compared with glucocorticoids alone. However, survival rates are not improved. Taxane-based combinations with estramustine phosphate or other new agents show promise. Prostate-specific antigen response rates with these combinations appear to be 1.5 to 2 times more frequent than with mitoxantrone-based combinations. Randomized trials of taxane versus mitoxantrone-based therapies are underway. New agents and applications of current agents in adjuvant settings should be explored if survival in men with prostate cancer is to be improved.
Chemotherapy of prostate cancer: Present and future Donald Trump1 and Yiu-Keung Lau1
Donald Trump1 and Yiu-Keung Lau1
(1) Department of Medicine, Roswell Park Cancer Institute, Elm and Carlton Streets, 14263 Buffalo, NY, USA
Abstract The role of chemotherapy in prostate cancer continues to evolve. In men with symptomatic androgen-independent prostate cancer, significant reduction in pain and analgesic requirements are achievable with mitoxantrone and glucocorticoid combinations compared with glucocorticoids alone. However, survival rates are not improved. Taxane-based combinations with estramustine phosphate or other new agents show promise. Prostate-specific antigen response rates with these combinations appear to be 1.5 to 2 times more frequent than with mitoxantrone-based combinations. Randomized trials of taxane versus mitoxantrone-based therapies are underway. New agents and applications of current agents in adjuvant settings should be explored if survival in men with prostate cancer is to be improved.
(1) Department of Medicine, Roswell Park Cancer Institute, Elm and Carlton Streets, 14263 Buffalo, NY, USA
Abstract The role of chemotherapy in prostate cancer continues to evolve. In men with symptomatic androgen-independent prostate cancer, significant reduction in pain and analgesic requirements are achievable with mitoxantrone and glucocorticoid combinations compared with glucocorticoids alone. However, survival rates are not improved. Taxane-based combinations with estramustine phosphate or other new agents show promise. Prostate-specific antigen response rates with these combinations appear to be 1.5 to 2 times more frequent than with mitoxantrone-based combinations. Randomized trials of taxane versus mitoxantrone-based therapies are underway. New agents and applications of current agents in adjuvant settings should be explored if survival in men with prostate cancer is to be improved.
Chemotherapy of metastatic colorectal cancer
Everardo D. Saad1 and Paulo M. Hoff1
(1) Department of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 426, 77030 Houston, TX, USA
Opinion statement Over the past decade, metastatic colorectal cancer has evolved from a relatively resistant disease to one that is sensitive to a variety of chemotherapeutic drugs and combinations of drugs. During the same period, the median survival of patients with metastatic colorectal cancer increased from approximately 14 months to almost 20 months. First-line chemotherapy prolongs survival and delays the appearance of symptoms and should be considered in patients who are still asymptomatic. Patients with metastatic colorectal cancer and adequate performance status should be treated with a combination of fluorouracil (5-FU) and either oxaliplatin or irinotecan. Bevacizumab, the monoclonal antibody against the vascular endothelial growth factor, has been shown to prolong survival with acceptable toxicity and may be added when available. When the disease recurs, second-line chemotherapy may also prolong survival in appropriately selected patients. Typically, treatment includes 5-FU and one of the drugs not used in the first-line therapy (oxaliplatin or irinotecan). Several oral prodrugs of 5-FU are currently available. Capecitabine, approved in the United States, may be safely substituted for 5-FU in the majority of settings and combinations. Cetuximab is a monoclonal antibody against the epidermal growth factor receptor and is approved both as a single agent and in combination with irinotecan for patients with recurrent disease. This treatment may represent a second-line or third-line option in selected patients. Treatment of patients with isolated liver metastases may also include surgical or other ablative procedures. In carefully selected patients, these modalities add to the efficacy of chemotherapy and may be used with potentially curative intent. However, for the vast majority of patients with metastatic colorectal cancer treatment is palliative.
(1) Department of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 426, 77030 Houston, TX, USA
Opinion statement Over the past decade, metastatic colorectal cancer has evolved from a relatively resistant disease to one that is sensitive to a variety of chemotherapeutic drugs and combinations of drugs. During the same period, the median survival of patients with metastatic colorectal cancer increased from approximately 14 months to almost 20 months. First-line chemotherapy prolongs survival and delays the appearance of symptoms and should be considered in patients who are still asymptomatic. Patients with metastatic colorectal cancer and adequate performance status should be treated with a combination of fluorouracil (5-FU) and either oxaliplatin or irinotecan. Bevacizumab, the monoclonal antibody against the vascular endothelial growth factor, has been shown to prolong survival with acceptable toxicity and may be added when available. When the disease recurs, second-line chemotherapy may also prolong survival in appropriately selected patients. Typically, treatment includes 5-FU and one of the drugs not used in the first-line therapy (oxaliplatin or irinotecan). Several oral prodrugs of 5-FU are currently available. Capecitabine, approved in the United States, may be safely substituted for 5-FU in the majority of settings and combinations. Cetuximab is a monoclonal antibody against the epidermal growth factor receptor and is approved both as a single agent and in combination with irinotecan for patients with recurrent disease. This treatment may represent a second-line or third-line option in selected patients. Treatment of patients with isolated liver metastases may also include surgical or other ablative procedures. In carefully selected patients, these modalities add to the efficacy of chemotherapy and may be used with potentially curative intent. However, for the vast majority of patients with metastatic colorectal cancer treatment is palliative.
Chemotherapy of metastatic colorectal cancer
Everardo D. Saad1 and Paulo M. Hoff1
(1) Department of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 426, 77030 Houston, TX, USA
Opinion statement Over the past decade, metastatic colorectal cancer has evolved from a relatively resistant disease to one that is sensitive to a variety of chemotherapeutic drugs and combinations of drugs. During the same period, the median survival of patients with metastatic colorectal cancer increased from approximately 14 months to almost 20 months. First-line chemotherapy prolongs survival and delays the appearance of symptoms and should be considered in patients who are still asymptomatic. Patients with metastatic colorectal cancer and adequate performance status should be treated with a combination of fluorouracil (5-FU) and either oxaliplatin or irinotecan. Bevacizumab, the monoclonal antibody against the vascular endothelial growth factor, has been shown to prolong survival with acceptable toxicity and may be added when available. When the disease recurs, second-line chemotherapy may also prolong survival in appropriately selected patients. Typically, treatment includes 5-FU and one of the drugs not used in the first-line therapy (oxaliplatin or irinotecan). Several oral prodrugs of 5-FU are currently available. Capecitabine, approved in the United States, may be safely substituted for 5-FU in the majority of settings and combinations. Cetuximab is a monoclonal antibody against the epidermal growth factor receptor and is approved both as a single agent and in combination with irinotecan for patients with recurrent disease. This treatment may represent a second-line or third-line option in selected patients. Treatment of patients with isolated liver metastases may also include surgical or other ablative procedures. In carefully selected patients, these modalities add to the efficacy of chemotherapy and may be used with potentially curative intent. However, for the vast majority of patients with metastatic colorectal cancer treatment is palliative.
(1) Department of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 426, 77030 Houston, TX, USA
Opinion statement Over the past decade, metastatic colorectal cancer has evolved from a relatively resistant disease to one that is sensitive to a variety of chemotherapeutic drugs and combinations of drugs. During the same period, the median survival of patients with metastatic colorectal cancer increased from approximately 14 months to almost 20 months. First-line chemotherapy prolongs survival and delays the appearance of symptoms and should be considered in patients who are still asymptomatic. Patients with metastatic colorectal cancer and adequate performance status should be treated with a combination of fluorouracil (5-FU) and either oxaliplatin or irinotecan. Bevacizumab, the monoclonal antibody against the vascular endothelial growth factor, has been shown to prolong survival with acceptable toxicity and may be added when available. When the disease recurs, second-line chemotherapy may also prolong survival in appropriately selected patients. Typically, treatment includes 5-FU and one of the drugs not used in the first-line therapy (oxaliplatin or irinotecan). Several oral prodrugs of 5-FU are currently available. Capecitabine, approved in the United States, may be safely substituted for 5-FU in the majority of settings and combinations. Cetuximab is a monoclonal antibody against the epidermal growth factor receptor and is approved both as a single agent and in combination with irinotecan for patients with recurrent disease. This treatment may represent a second-line or third-line option in selected patients. Treatment of patients with isolated liver metastases may also include surgical or other ablative procedures. In carefully selected patients, these modalities add to the efficacy of chemotherapy and may be used with potentially curative intent. However, for the vast majority of patients with metastatic colorectal cancer treatment is palliative.
Chemotherapy of colorectal cancer
Susan Partyka1 and Jaffer Ajani1
(1) Division of Medicine, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Box 78, 77030 Houston, Texas
Opinion Statement – Progress has been made in the adjuvant treatment of colorectal carcinoma.
– The improvement in survival with the use of adjuvant 5-FU and leucovorin in patients with stage III colon carcinoma has been readily established. However, a survival benefit in stage II patients treated with adjuvant therapy remains unproven. Further evaluation using additional/new prognostic factors may identify a high-risk stage II group that would benefit from adjuvant treatment.
– Adjuvant chemoradiation has become standard therapy for stage II and III patients with rectal carcinoma. Investigations using preoperative combined-modality therapy are being explored to assess sphincter preservation rates and to evaluate any impact on survival. Radiosensitizing chemotherapeutic agents need to be evaluated in this patient population.
– Recent advances in metastatic disease have occurred. Frontline therapy remains 5-FU and leucovorin. CPT-11 has demonstrated responses in 5-FU relapsed and refractory patients and is the new standard therapy in these patients. New data recently available also show a survival advantage in patients treated with CPT-11 versus supportive care in 5-FU and leucovorin failures.
– New agents such as UFT and oxaliplatin have demonstrated activity in colorectal carcinomas and in the future these agents will likely aid in the treatment of this disease.
(1) Division of Medicine, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Box 78, 77030 Houston, Texas
Opinion Statement – Progress has been made in the adjuvant treatment of colorectal carcinoma.
– The improvement in survival with the use of adjuvant 5-FU and leucovorin in patients with stage III colon carcinoma has been readily established. However, a survival benefit in stage II patients treated with adjuvant therapy remains unproven. Further evaluation using additional/new prognostic factors may identify a high-risk stage II group that would benefit from adjuvant treatment.
– Adjuvant chemoradiation has become standard therapy for stage II and III patients with rectal carcinoma. Investigations using preoperative combined-modality therapy are being explored to assess sphincter preservation rates and to evaluate any impact on survival. Radiosensitizing chemotherapeutic agents need to be evaluated in this patient population.
– Recent advances in metastatic disease have occurred. Frontline therapy remains 5-FU and leucovorin. CPT-11 has demonstrated responses in 5-FU relapsed and refractory patients and is the new standard therapy in these patients. New data recently available also show a survival advantage in patients treated with CPT-11 versus supportive care in 5-FU and leucovorin failures.
– New agents such as UFT and oxaliplatin have demonstrated activity in colorectal carcinomas and in the future these agents will likely aid in the treatment of this disease.
Chemotherapy intensification
Gianluca Masi and Alfredo Falcone1
(1) Department of Oncology, Azienda USL-6 of Livorno Viale Alfieri, 36, 57124 Livorno, Italy
Published online: 8 July 2007
Abstract Today the treatment of metastatic colorectal cancer is based on several treatment options incorporating chemotherapy, targeted agents, and the surgery of metastases, and a median survival of almost 2 years has been reached. Despite these advances and the availability of multiple lines of treatment, the choice of the first-line chemotherapy indeed still matters, and the development of chemotherapy regimens associated with improved efficacy is a key question in the “biologics era.” This review discusses the development of the triple drug combination FOLFOXIRI (irinotecan [CPT-11], oxaliplatin, and 5-fluorouracil [5FU]/leucovorin [LV]). Several phase II trials demonstrated the feasibility of this combination and, more importantly, a phase III trial demonstrated that the triplet FOLFOXIRI is the first studied combination that significantly increases response rate, complete tumor resection of metastases, progression-free survival, and overall survival compared with an infusional 5FU containing doublet, such as FOLFIRI (5FU/LV and CPT-11). Therefore, FOLFOXIRI represents a new first-line option of care for patients with metastatic colorectal cancer.
(1) Department of Oncology, Azienda USL-6 of Livorno Viale Alfieri, 36, 57124 Livorno, Italy
Published online: 8 July 2007
Abstract Today the treatment of metastatic colorectal cancer is based on several treatment options incorporating chemotherapy, targeted agents, and the surgery of metastases, and a median survival of almost 2 years has been reached. Despite these advances and the availability of multiple lines of treatment, the choice of the first-line chemotherapy indeed still matters, and the development of chemotherapy regimens associated with improved efficacy is a key question in the “biologics era.” This review discusses the development of the triple drug combination FOLFOXIRI (irinotecan [CPT-11], oxaliplatin, and 5-fluorouracil [5FU]/leucovorin [LV]). Several phase II trials demonstrated the feasibility of this combination and, more importantly, a phase III trial demonstrated that the triplet FOLFOXIRI is the first studied combination that significantly increases response rate, complete tumor resection of metastases, progression-free survival, and overall survival compared with an infusional 5FU containing doublet, such as FOLFIRI (5FU/LV and CPT-11). Therefore, FOLFOXIRI represents a new first-line option of care for patients with metastatic colorectal cancer.
Wolfgang Lilleby1 and Sophie D. Fosså1
Mohamed Hebbar1
(1) Unité d’Oncologie Médicale, Hôpital Huriez, CHRU, 1 rue Michel Polonovski, 59037 Lille, France
Abstract New chemotherapy drugs and, more recently, targeted therapies have significantly improved the outcome of patients with resected stage III colon cancer (adjuvant chemotherapy) and patients with unresectable metastases (palliative therapy). These advances raise several questions about the place of chemotherapy after and before surgery in patients with resectable liver metastases. To date, only a combined intra-arterial plus systemic fluoropyrimidine-based chemotherapy regimen has clearly demonstrated a relapse-free survival benefit. Yet, this approach is restricted to specialized centers, mainly because of technical difficulties and locoregional toxicities. The role of systemic use of oxaliplatin- and irinotecan-based regimens is currently under investigation. Planned trials will assess the role of anti-angiogenic and anti-epidermal growth factor receptor agents. We review the main trials performed in patients with resectable metastases, and discuss their potent impact on clinical practice.
(1) Unité d’Oncologie Médicale, Hôpital Huriez, CHRU, 1 rue Michel Polonovski, 59037 Lille, France
Abstract New chemotherapy drugs and, more recently, targeted therapies have significantly improved the outcome of patients with resected stage III colon cancer (adjuvant chemotherapy) and patients with unresectable metastases (palliative therapy). These advances raise several questions about the place of chemotherapy after and before surgery in patients with resectable liver metastases. To date, only a combined intra-arterial plus systemic fluoropyrimidine-based chemotherapy regimen has clearly demonstrated a relapse-free survival benefit. Yet, this approach is restricted to specialized centers, mainly because of technical difficulties and locoregional toxicities. The role of systemic use of oxaliplatin- and irinotecan-based regimens is currently under investigation. Planned trials will assess the role of anti-angiogenic and anti-epidermal growth factor receptor agents. We review the main trials performed in patients with resectable metastases, and discuss their potent impact on clinical practice.
Chemotherapy in metastatic renal cell cancer
Wolfgang Lilleby1 and Sophie D. Fosså1
(1) Department of Medical Oncology and Radiotherapy, The Norwegian Radium University Hospital, Oslo, Norway
Received: 15 November 2004 Accepted: 15 November 2004 Published online: 22 February 2005
Abstract Currently, there is no standard treatment for patients with advanced renal cell carcinoma (RCC) who do not respond to or progress after transient remission to first-line immunotherapy. At the end of the 1990s, no single chemotherapeutic drug, alone or in combination with interleukin-2 (IL-2) or interferon-alfa (IFN), had shown activity beyond the one expected by immunotherapy alone. New drugs on the market such as the pyrimidine analog gemcitabine or taxane-based chemotherapeutics may show promising tumor activity in combination with targeted therapy, but this has to be substantiated in upcoming trials. There is a great need to develop effective systemic therapy for advanced MRCC and to evaluate the efficacy of new drugs in clinical trials.
Keywords Chemotherapy - Renal cell cancer - Cytokines - Drug resistance
(1) Department of Medical Oncology and Radiotherapy, The Norwegian Radium University Hospital, Oslo, Norway
Received: 15 November 2004 Accepted: 15 November 2004 Published online: 22 February 2005
Abstract Currently, there is no standard treatment for patients with advanced renal cell carcinoma (RCC) who do not respond to or progress after transient remission to first-line immunotherapy. At the end of the 1990s, no single chemotherapeutic drug, alone or in combination with interleukin-2 (IL-2) or interferon-alfa (IFN), had shown activity beyond the one expected by immunotherapy alone. New drugs on the market such as the pyrimidine analog gemcitabine or taxane-based chemotherapeutics may show promising tumor activity in combination with targeted therapy, but this has to be substantiated in upcoming trials. There is a great need to develop effective systemic therapy for advanced MRCC and to evaluate the efficacy of new drugs in clinical trials.
Keywords Chemotherapy - Renal cell cancer - Cytokines - Drug resistance
Chemotherapy in metastatic colorectal cancer
A. Christopoulou1
(1) Section of Oncology, St. Andrews General Hospital, Votsi 31–33, 262-21 Patras, Greece
Abstract The treatment of patients with metastatic colorectal cancer (MCRC) has changed dramatically over the years. 5-Fluorouracil (5FU)-based therapies have been routinely included in treatment regimens for colorectal cancer for the past 40 years. Anumber of options are available to clinicians for the treatment of patients relapsing after surgical excision of their primary tumour, such as 5FU in association with FA, the new drugs such as irinotecan and oxaliplatin and the oral fluoropyrimidines: capecitabine and uracil/tegafur (UFT). It has been shown that combination therapy with 5FU/FA and irinotecan or oxaliplatin is more active than 5FU/FA in the first line of treatment in MCRC. New agents acting on novel targets are under development such as epidermal growth factor inhibitors, vascular endothelial growth factor inhibitors and cyclooxygenase 2 inhibitors.
(1) Section of Oncology, St. Andrews General Hospital, Votsi 31–33, 262-21 Patras, Greece
Abstract The treatment of patients with metastatic colorectal cancer (MCRC) has changed dramatically over the years. 5-Fluorouracil (5FU)-based therapies have been routinely included in treatment regimens for colorectal cancer for the past 40 years. Anumber of options are available to clinicians for the treatment of patients relapsing after surgical excision of their primary tumour, such as 5FU in association with FA, the new drugs such as irinotecan and oxaliplatin and the oral fluoropyrimidines: capecitabine and uracil/tegafur (UFT). It has been shown that combination therapy with 5FU/FA and irinotecan or oxaliplatin is more active than 5FU/FA in the first line of treatment in MCRC. New agents acting on novel targets are under development such as epidermal growth factor inhibitors, vascular endothelial growth factor inhibitors and cyclooxygenase 2 inhibitors.
Chemotherapy for prostate cancer: implementing early systemic therapy to improve outcomes
Gary R. MacVicar2 and Maha Hussain1
(1) University of Michigan Comprehensive Cancer Center, 7314 CCGC, 1500 E. Medical Center Drive, Ann Arbor, MI 48109-0946, USA
(2) Division of Hematology/Oncology, Northwestern University, Chicago, IL 60611, USA
Published online: 5 November 2005
Abstract Prostate cancer remains a significant health concern for men in the USA as it is a leading cancer diagnosis and a cause of death. With the use of prostate-specific antigen or screening, a stage migration has occurred with an increase in the number of men diagnosed with early-stage disease. The optimal primary management of these men is evolving, but despite adequate local treatment a significant percentage will develop either biochemical or clinical evidence of recurrent disease. Several criteria for risk stratification have been developed, thus, improving the ability to identify a high-risk population. Small studies have been reported demonstrating the feasibility of neoadjuvant or adjuvant chemotherapy in conjunction with either radiation or radical prostatectomy in this high-risk population, and large phase III studies are ongoing. With the advent of life-prolonging chemotherapy in the hormone-refractory setting, attention must now also be given to early-stage disease so as to develop multi-modality approaches with the hope of increasing survival and ultimately providing a cure.
Keywords Prostate cancer - Adjuvant therapy - Neoadjuvant therapy - Multimodality therapy - Chemotherapy
(1) University of Michigan Comprehensive Cancer Center, 7314 CCGC, 1500 E. Medical Center Drive, Ann Arbor, MI 48109-0946, USA
(2) Division of Hematology/Oncology, Northwestern University, Chicago, IL 60611, USA
Published online: 5 November 2005
Abstract Prostate cancer remains a significant health concern for men in the USA as it is a leading cancer diagnosis and a cause of death. With the use of prostate-specific antigen or screening, a stage migration has occurred with an increase in the number of men diagnosed with early-stage disease. The optimal primary management of these men is evolving, but despite adequate local treatment a significant percentage will develop either biochemical or clinical evidence of recurrent disease. Several criteria for risk stratification have been developed, thus, improving the ability to identify a high-risk population. Small studies have been reported demonstrating the feasibility of neoadjuvant or adjuvant chemotherapy in conjunction with either radiation or radical prostatectomy in this high-risk population, and large phase III studies are ongoing. With the advent of life-prolonging chemotherapy in the hormone-refractory setting, attention must now also be given to early-stage disease so as to develop multi-modality approaches with the hope of increasing survival and ultimately providing a cure.
Keywords Prostate cancer - Adjuvant therapy - Neoadjuvant therapy - Multimodality therapy - Chemotherapy
Chemotherapy for cervical cancer
Isabelle Cadron1, Frederic Amant1 and Ignace Vergote1
(1) Division of Gynecological Oncology, Department of Obstetrics and Gynecology, University Hospitals Leuven, Leuven, Belgium
Received: 11 September 2005 Accepted: 30 September 2005 Published online: 22 November 2005
Abstract Therapeutic options for cervical cancer have improved extensively over the last decade with the introduction of neoadjuvant chemotherapy prior to surgery for stage IB2–IIB and chemoradiation (radiation with concomitant weekly cisplatinum). Both regimens showed an improvement in overall survival of 14 and 12%, respectively, in comparison with radiotherapy alone. As for metastatic or recurrent cervical cancer, chemotherapy regimens are changing from cisplatin only to combination chemotherapy. Cisplatin with topotecan is the first combination regimen that showed an improvement in overall survival. However, further randomized trials will be necessary to confirm the superiority of this combination.
Keywords Cervical carcinoma - Neoplasms - Uterine - Chemotherapy
(1) Division of Gynecological Oncology, Department of Obstetrics and Gynecology, University Hospitals Leuven, Leuven, Belgium
Received: 11 September 2005 Accepted: 30 September 2005 Published online: 22 November 2005
Abstract Therapeutic options for cervical cancer have improved extensively over the last decade with the introduction of neoadjuvant chemotherapy prior to surgery for stage IB2–IIB and chemoradiation (radiation with concomitant weekly cisplatinum). Both regimens showed an improvement in overall survival of 14 and 12%, respectively, in comparison with radiotherapy alone. As for metastatic or recurrent cervical cancer, chemotherapy regimens are changing from cisplatin only to combination chemotherapy. Cisplatin with topotecan is the first combination regimen that showed an improvement in overall survival. However, further randomized trials will be necessary to confirm the superiority of this combination.
Keywords Cervical carcinoma - Neoplasms - Uterine - Chemotherapy
Chemotherapy in patients with resectable liver metastases from colorectal cancer
Mohamed Hebbar1
(1) Unité d’Oncologie Médicale, Hôpital Huriez, CHRU, 1 rue Michel Polonovski, 59037 Lille, France
Abstract New chemotherapy drugs and, more recently, targeted therapies have significantly improved the outcome of patients with resected stage III colon cancer (adjuvant chemotherapy) and patients with unresectable metastases (palliative therapy). These advances raise several questions about the place of chemotherapy after and before surgery in patients with resectable liver metastases. To date, only a combined intra-arterial plus systemic fluoropyrimidine-based chemotherapy regimen has clearly demonstrated a relapse-free survival benefit. Yet, this approach is restricted to specialized centers, mainly because of technical difficulties and locoregional toxicities. The role of systemic use of oxaliplatin- and irinotecan-based regimens is currently under investigation. Planned trials will assess the role of anti-angiogenic and anti-epidermal growth factor receptor agents. We review the main trials performed in patients with resectable metastases, and discuss their potent impact on clinical practice.
(1) Unité d’Oncologie Médicale, Hôpital Huriez, CHRU, 1 rue Michel Polonovski, 59037 Lille, France
Abstract New chemotherapy drugs and, more recently, targeted therapies have significantly improved the outcome of patients with resected stage III colon cancer (adjuvant chemotherapy) and patients with unresectable metastases (palliative therapy). These advances raise several questions about the place of chemotherapy after and before surgery in patients with resectable liver metastases. To date, only a combined intra-arterial plus systemic fluoropyrimidine-based chemotherapy regimen has clearly demonstrated a relapse-free survival benefit. Yet, this approach is restricted to specialized centers, mainly because of technical difficulties and locoregional toxicities. The role of systemic use of oxaliplatin- and irinotecan-based regimens is currently under investigation. Planned trials will assess the role of anti-angiogenic and anti-epidermal growth factor receptor agents. We review the main trials performed in patients with resectable metastases, and discuss their potent impact on clinical practice.
Chemotherapy in metastatic renal cell cancer
Wolfgang Lilleby1 and Sophie D. Fosså1
(1) Department of Medical Oncology and Radiotherapy, The Norwegian Radium University Hospital, Oslo, Norway
Received: 15 November 2004 Accepted: 15 November 2004 Published online: 22 February 2005
Abstract Currently, there is no standard treatment for patients with advanced renal cell carcinoma (RCC) who do not respond to or progress after transient remission to first-line immunotherapy. At the end of the 1990s, no single chemotherapeutic drug, alone or in combination with interleukin-2 (IL-2) or interferon-alfa (IFN), had shown activity beyond the one expected by immunotherapy alone. New drugs on the market such as the pyrimidine analog gemcitabine or taxane-based chemotherapeutics may show promising tumor activity in combination with targeted therapy, but this has to be substantiated in upcoming trials. There is a great need to develop effective systemic therapy for advanced MRCC and to evaluate the efficacy of new drugs in clinical trials.
Keywords Chemotherapy - Renal cell cancer - Cytokines - Drug resistance
(1) Department of Medical Oncology and Radiotherapy, The Norwegian Radium University Hospital, Oslo, Norway
Received: 15 November 2004 Accepted: 15 November 2004 Published online: 22 February 2005
Abstract Currently, there is no standard treatment for patients with advanced renal cell carcinoma (RCC) who do not respond to or progress after transient remission to first-line immunotherapy. At the end of the 1990s, no single chemotherapeutic drug, alone or in combination with interleukin-2 (IL-2) or interferon-alfa (IFN), had shown activity beyond the one expected by immunotherapy alone. New drugs on the market such as the pyrimidine analog gemcitabine or taxane-based chemotherapeutics may show promising tumor activity in combination with targeted therapy, but this has to be substantiated in upcoming trials. There is a great need to develop effective systemic therapy for advanced MRCC and to evaluate the efficacy of new drugs in clinical trials.
Keywords Chemotherapy - Renal cell cancer - Cytokines - Drug resistance
Head and neck cancer: the possible role of stem cells
C. Bianchini1 , A. Ciorba1, S. Pelucchi1, R. Piva1, 2 and A. Pastore1
(1) ENT Department, University Hospital of Ferrara, C.so Giovecca 203, 44100 Ferrara, Italy
(2) Molecular Biology Section, Department of Biochemistry and Molecular Biology, University of Ferrara, Ferrara, Italy
Received: 16 June 2007 Accepted: 20 September 2007 Published online: 13 October 2007
Abstract There is a rising interest in the field of oncology in order to understand if cancer stem cells can play a key role also in the pathogenesis of head and neck tumors. It is likely that cancer stem cells are a minor population of tumor cells that possess the stem cell property of self-renewal. In addition, dysregulation of stem cell self-renewal is a likely requirement for the development of cancer. This new model for cancer will have significant ramifications for the way we will study and treat tumors. The authors are proposing a discussion of this topic, which, in their opinion, need to be further investigated in the ENT field.
Keywords Cancer - Stem cells - Head and neck
Bianchini and Ciorba have equally contributed to the paper.
(1) ENT Department, University Hospital of Ferrara, C.so Giovecca 203, 44100 Ferrara, Italy
(2) Molecular Biology Section, Department of Biochemistry and Molecular Biology, University of Ferrara, Ferrara, Italy
Received: 16 June 2007 Accepted: 20 September 2007 Published online: 13 October 2007
Abstract There is a rising interest in the field of oncology in order to understand if cancer stem cells can play a key role also in the pathogenesis of head and neck tumors. It is likely that cancer stem cells are a minor population of tumor cells that possess the stem cell property of self-renewal. In addition, dysregulation of stem cell self-renewal is a likely requirement for the development of cancer. This new model for cancer will have significant ramifications for the way we will study and treat tumors. The authors are proposing a discussion of this topic, which, in their opinion, need to be further investigated in the ENT field.
Keywords Cancer - Stem cells - Head and neck
Bianchini and Ciorba have equally contributed to the paper.
Chemotherapy in metastatic colorectal cancer
A. Christopoulou1
(1) Section of Oncology, St. Andrews General Hospital, Votsi 31–33, 262-21 Patras, Greece
Abstract The treatment of patients with metastatic colorectal cancer (MCRC) has changed dramatically over the years. 5-Fluorouracil (5FU)-based therapies have been routinely included in treatment regimens for colorectal cancer for the past 40 years. Anumber of options are available to clinicians for the treatment of patients relapsing after surgical excision of their primary tumour, such as 5FU in association with FA, the new drugs such as irinotecan and oxaliplatin and the oral fluoropyrimidines: capecitabine and uracil/tegafur (UFT). It has been shown that combination therapy with 5FU/FA and irinotecan or oxaliplatin is more active than 5FU/FA in the first line of treatment in MCRC. New agents acting on novel targets are under development such as epidermal growth factor inhibitors, vascular endothelial growth factor inhibitors and cyclooxygenase 2 inhibitors.
(1) Section of Oncology, St. Andrews General Hospital, Votsi 31–33, 262-21 Patras, Greece
Abstract The treatment of patients with metastatic colorectal cancer (MCRC) has changed dramatically over the years. 5-Fluorouracil (5FU)-based therapies have been routinely included in treatment regimens for colorectal cancer for the past 40 years. Anumber of options are available to clinicians for the treatment of patients relapsing after surgical excision of their primary tumour, such as 5FU in association with FA, the new drugs such as irinotecan and oxaliplatin and the oral fluoropyrimidines: capecitabine and uracil/tegafur (UFT). It has been shown that combination therapy with 5FU/FA and irinotecan or oxaliplatin is more active than 5FU/FA in the first line of treatment in MCRC. New agents acting on novel targets are under development such as epidermal growth factor inhibitors, vascular endothelial growth factor inhibitors and cyclooxygenase 2 inhibitors.
Common Molecular Mechanisms of Mammary Gland Development and Breast Cancer
K. Lundgren1, C. Holm1 and G. Landberg1
(1) Center for Molecular Pathology, Department of Laboratory Medicine, Lund University, Malmö University Hospital, S-205 02 Malmö, Sweden
Published online: 22 October 2007
Abstract. Hypoxia affects many important processes in tumour progression and is a key feature in the tumour microenvironment that needs to be taken into account when evaluating prognostics and therapeutic options for cancer patients. Hypoxia-regulating proteins, i.e. hypoxia inducible factors (HIFs), and associated gene products have been linked to certain tumour behaviours and might be useful as prognostic and predictive markers. Recently, hypoxia-driven gene products have been launched as novel cancer treatment targets with the potential to increase tumour-specific effects. Breast cancer consists of a multitude of different diseases with certain common characteristics, but also clearly disparate behaviours and genetic alterations. In this review we will summarise the role of hypoxia in breast cancer and specifically outline the importance of hypoxia and HIF-1α regarding prognostic and treatment-specific implications. (Part of a Multi-author Review)
Keywords. Breast cancer - HIF-1α - hypoxia - prognosis - treatment
(1) Center for Molecular Pathology, Department of Laboratory Medicine, Lund University, Malmö University Hospital, S-205 02 Malmö, Sweden
Published online: 22 October 2007
Abstract. Hypoxia affects many important processes in tumour progression and is a key feature in the tumour microenvironment that needs to be taken into account when evaluating prognostics and therapeutic options for cancer patients. Hypoxia-regulating proteins, i.e. hypoxia inducible factors (HIFs), and associated gene products have been linked to certain tumour behaviours and might be useful as prognostic and predictive markers. Recently, hypoxia-driven gene products have been launched as novel cancer treatment targets with the potential to increase tumour-specific effects. Breast cancer consists of a multitude of different diseases with certain common characteristics, but also clearly disparate behaviours and genetic alterations. In this review we will summarise the role of hypoxia in breast cancer and specifically outline the importance of hypoxia and HIF-1α regarding prognostic and treatment-specific implications. (Part of a Multi-author Review)
Keywords. Breast cancer - HIF-1α - hypoxia - prognosis - treatment
Chemotherapy for prostate cancer: implementing early systemic therapy to improve outcomes
Gary R. MacVicar2 and Maha Hussain1
(1) University of Michigan Comprehensive Cancer Center, 7314 CCGC, 1500 E. Medical Center Drive, Ann Arbor, MI 48109-0946, USA
(2) Division of Hematology/Oncology, Northwestern University, Chicago, IL 60611, USA
Published online: 5 November 2005
Abstract Prostate cancer remains a significant health concern for men in the USA as it is a leading cancer diagnosis and a cause of death. With the use of prostate-specific antigen or screening, a stage migration has occurred with an increase in the number of men diagnosed with early-stage disease. The optimal primary management of these men is evolving, but despite adequate local treatment a significant percentage will develop either biochemical or clinical evidence of recurrent disease. Several criteria for risk stratification have been developed, thus, improving the ability to identify a high-risk population. Small studies have been reported demonstrating the feasibility of neoadjuvant or adjuvant chemotherapy in conjunction with either radiation or radical prostatectomy in this high-risk population, and large phase III studies are ongoing. With the advent of life-prolonging chemotherapy in the hormone-refractory setting, attention must now also be given to early-stage disease so as to develop multi-modality approaches with the hope of increasing survival and ultimately providing a cure.
Keywords Prostate cancer - Adjuvant therapy - Neoadjuvant therapy - Multimodality therapy - Chemotherapy
(1) University of Michigan Comprehensive Cancer Center, 7314 CCGC, 1500 E. Medical Center Drive, Ann Arbor, MI 48109-0946, USA
(2) Division of Hematology/Oncology, Northwestern University, Chicago, IL 60611, USA
Published online: 5 November 2005
Abstract Prostate cancer remains a significant health concern for men in the USA as it is a leading cancer diagnosis and a cause of death. With the use of prostate-specific antigen or screening, a stage migration has occurred with an increase in the number of men diagnosed with early-stage disease. The optimal primary management of these men is evolving, but despite adequate local treatment a significant percentage will develop either biochemical or clinical evidence of recurrent disease. Several criteria for risk stratification have been developed, thus, improving the ability to identify a high-risk population. Small studies have been reported demonstrating the feasibility of neoadjuvant or adjuvant chemotherapy in conjunction with either radiation or radical prostatectomy in this high-risk population, and large phase III studies are ongoing. With the advent of life-prolonging chemotherapy in the hormone-refractory setting, attention must now also be given to early-stage disease so as to develop multi-modality approaches with the hope of increasing survival and ultimately providing a cure.
Keywords Prostate cancer - Adjuvant therapy - Neoadjuvant therapy - Multimodality therapy - Chemotherapy
Head and neck cancer: the possible role of stem cells
C. Bianchini1 , A. Ciorba1, S. Pelucchi1, R. Piva1, 2 and A. Pastore1
(1) ENT Department, University Hospital of Ferrara, C.so Giovecca 203, 44100 Ferrara, Italy
(2) Molecular Biology Section, Department of Biochemistry and Molecular Biology, University of Ferrara, Ferrara, Italy
Received: 16 June 2007 Accepted: 20 September 2007 Published online: 13 October 2007
Abstract There is a rising interest in the field of oncology in order to understand if cancer stem cells can play a key role also in the pathogenesis of head and neck tumors. It is likely that cancer stem cells are a minor population of tumor cells that possess the stem cell property of self-renewal. In addition, dysregulation of stem cell self-renewal is a likely requirement for the development of cancer. This new model for cancer will have significant ramifications for the way we will study and treat tumors. The authors are proposing a discussion of this topic, which, in their opinion, need to be further investigated in the ENT field.
Keywords Cancer - Stem cells - Head and neck
Bianchini and Ciorba have equally contributed to the paper.
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(1) ENT Department, University Hospital of Ferrara, C.so Giovecca 203, 44100 Ferrara, Italy
(2) Molecular Biology Section, Department of Biochemistry and Molecular Biology, University of Ferrara, Ferrara, Italy
Received: 16 June 2007 Accepted: 20 September 2007 Published online: 13 October 2007
Abstract There is a rising interest in the field of oncology in order to understand if cancer stem cells can play a key role also in the pathogenesis of head and neck tumors. It is likely that cancer stem cells are a minor population of tumor cells that possess the stem cell property of self-renewal. In addition, dysregulation of stem cell self-renewal is a likely requirement for the development of cancer. This new model for cancer will have significant ramifications for the way we will study and treat tumors. The authors are proposing a discussion of this topic, which, in their opinion, need to be further investigated in the ENT field.
Keywords Cancer - Stem cells - Head and neck
Bianchini and Ciorba have equally contributed to the paper.
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Chemotherapy for cervical cancer
Isabelle Cadron1, Frederic Amant1 and Ignace Vergote1
(1) Division of Gynecological Oncology, Department of Obstetrics and Gynecology, University Hospitals Leuven, Leuven, Belgium
Received: 11 September 2005 Accepted: 30 September 2005 Published online: 22 November 2005
Abstract Therapeutic options for cervical cancer have improved extensively over the last decade with the introduction of neoadjuvant chemotherapy prior to surgery for stage IB2–IIB and chemoradiation (radiation with concomitant weekly cisplatinum). Both regimens showed an improvement in overall survival of 14 and 12%, respectively, in comparison with radiotherapy alone. As for metastatic or recurrent cervical cancer, chemotherapy regimens are changing from cisplatin only to combination chemotherapy. Cisplatin with topotecan is the first combination regimen that showed an improvement in overall survival. However, further randomized trials will be necessary to confirm the superiority of this combination.
Keywords Cervical carcinoma - Neoplasms - Uterine - Chemotherapy
(1) Division of Gynecological Oncology, Department of Obstetrics and Gynecology, University Hospitals Leuven, Leuven, Belgium
Received: 11 September 2005 Accepted: 30 September 2005 Published online: 22 November 2005
Abstract Therapeutic options for cervical cancer have improved extensively over the last decade with the introduction of neoadjuvant chemotherapy prior to surgery for stage IB2–IIB and chemoradiation (radiation with concomitant weekly cisplatinum). Both regimens showed an improvement in overall survival of 14 and 12%, respectively, in comparison with radiotherapy alone. As for metastatic or recurrent cervical cancer, chemotherapy regimens are changing from cisplatin only to combination chemotherapy. Cisplatin with topotecan is the first combination regimen that showed an improvement in overall survival. However, further randomized trials will be necessary to confirm the superiority of this combination.
Keywords Cervical carcinoma - Neoplasms - Uterine - Chemotherapy
Neutrophils and TRAIL: insights into BCG immunotherapy for bladder cancer
Mark P. Simons1, 2, William M. Nauseef2, 3, 4, 5 and Thomas S. Griffith1, 4
(1) Department of Urology, 3204 MERF, University of Iowa, 375 Newton Road, Iowa City, IA 52242-1089, USA
(2) Inflammation Program, University of Iowa, Iowa City, IA, USA
(3) Department of Medicine, University of Iowa, Iowa City, IA, USA
(4) Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, IA, USA
(5) VA Medical Center, Iowa City, IA, USA
Published online: 19 June 2007
Abstract Bladder cancer is a huge economic burden on the healthcare system and is responsible for approximately 5% of all cancer deaths in humans. Mycobacterium bovis BCG-based therapy is the treatment of choice for superficial bladder cancer. Bacillus Calmette-Guerin (BCG) instillation in the bladder results in a massive local inflammatory response that has secondary antitumor properties. Recent studies have demonstrated that neutrophils present in the bladder after BCG instillation release large amounts of the apoptosis-inducing molecule TRAIL, as well as chemokines that recruit other immune cells, suggesting that neutrophils play a key role in the antitumor response to BCG therapy. This review discusses the impact of these findings on the understanding of the antitumor mechanisms underlying BCG-based immunotherapy for bladder cancer.
Keywords TRAIL - Neutrophil - PMN - BCG - Mycobacterium
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(1) Department of Urology, 3204 MERF, University of Iowa, 375 Newton Road, Iowa City, IA 52242-1089, USA
(2) Inflammation Program, University of Iowa, Iowa City, IA, USA
(3) Department of Medicine, University of Iowa, Iowa City, IA, USA
(4) Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, IA, USA
(5) VA Medical Center, Iowa City, IA, USA
Published online: 19 June 2007
Abstract Bladder cancer is a huge economic burden on the healthcare system and is responsible for approximately 5% of all cancer deaths in humans. Mycobacterium bovis BCG-based therapy is the treatment of choice for superficial bladder cancer. Bacillus Calmette-Guerin (BCG) instillation in the bladder results in a massive local inflammatory response that has secondary antitumor properties. Recent studies have demonstrated that neutrophils present in the bladder after BCG instillation release large amounts of the apoptosis-inducing molecule TRAIL, as well as chemokines that recruit other immune cells, suggesting that neutrophils play a key role in the antitumor response to BCG therapy. This review discusses the impact of these findings on the understanding of the antitumor mechanisms underlying BCG-based immunotherapy for bladder cancer.
Keywords TRAIL - Neutrophil - PMN - BCG - Mycobacterium
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Adjuvant therapy of colon cancer in idiopathic leukopenia
Weijing Sun1 and Daniel G. Haller1
(1) Abramson Cancer Center, University of Pennsylvania, 16 Penn Tower, 3400 Spruce Street, 19104-4283 Philadelphia, PA, USA
Abstract As there have been advances in the treatment of metastatic colorectal cancer, exciting developments have also been achieved in the adjuvant treatment of colon cancer. At the same time, more questions have been raised, and some controversies remain. The results of the MOSAIC trial demonstrated the benefit of adding oxaliplatin to 5-fluorouracil (5-FU) and leucovorin (FOLFOX) in adjuvant therapy for stage II and III disease, but the optimal duration of therapy and the management of toxicities remain to be resolved. Capecitabine is at least equivalent to the Mayo Clinic bolus 5-FU and leucovorin regimen in the adjuvant treatment of stage III colon cancer with a lower incidence profile of adverse events, allowing additional options for patients and physicians. Routine adjuvant systemic therapy in all patients with stage II colon cancer is still debatable. Although a statistically significant advantage for adjuvant treatment in stage II disease was shown for the first time from a large randomized study (QUASAR), the subsets of patients who truly benefit from therapy need to be identified. The application of pharmacogenetics and pharmacogenomics in adjuvant therapy for colorectal cancer will help to distinguish those patients with risk factors and to guide individualized therapy.
(1) Abramson Cancer Center, University of Pennsylvania, 16 Penn Tower, 3400 Spruce Street, 19104-4283 Philadelphia, PA, USA
Abstract As there have been advances in the treatment of metastatic colorectal cancer, exciting developments have also been achieved in the adjuvant treatment of colon cancer. At the same time, more questions have been raised, and some controversies remain. The results of the MOSAIC trial demonstrated the benefit of adding oxaliplatin to 5-fluorouracil (5-FU) and leucovorin (FOLFOX) in adjuvant therapy for stage II and III disease, but the optimal duration of therapy and the management of toxicities remain to be resolved. Capecitabine is at least equivalent to the Mayo Clinic bolus 5-FU and leucovorin regimen in the adjuvant treatment of stage III colon cancer with a lower incidence profile of adverse events, allowing additional options for patients and physicians. Routine adjuvant systemic therapy in all patients with stage II colon cancer is still debatable. Although a statistically significant advantage for adjuvant treatment in stage II disease was shown for the first time from a large randomized study (QUASAR), the subsets of patients who truly benefit from therapy need to be identified. The application of pharmacogenetics and pharmacogenomics in adjuvant therapy for colorectal cancer will help to distinguish those patients with risk factors and to guide individualized therapy.
Chemotherapy for androgenindependent prostate cancer: Myth or reality
Wm. Kevin Kelly1 and Susan F. Slovin1
(1) Genitourinary Oncology Service, Division of Solid Tumor Oncology, Memorial Sloan-Kettering Cancer Center, and Department of Medicine, Joan and Sanford Weill Medical College of Cornell University, 1275 York Avenue, 10021 New York, NY, USA
Abstract In the past, the treatment options for patients with metastatic prostate cancer that progressed despite castrate levels of testosterone was limited, and no therapies provided an improvement in survival. The majority of these patients had extensive osseous disease, multiple comorbidities, and poor performance status. With the widespread use of prostate-specific antigen (PSA) to monitor their clinical course, patients have presented with less extensive disease and a better performance status. Clinical trial methodology has improved as well, through incorporation of post-therapy changes in PSA to evaluate novel agents. This approach allows more patients to enter clinical trials, and the results show that the majority of these patients will have significant reduction in pain, regression of measurable disease, and suppression of PSA. These data suggest that prostate cancer is not as resistant to chemotherapy as it was once thought to be.
(1) Genitourinary Oncology Service, Division of Solid Tumor Oncology, Memorial Sloan-Kettering Cancer Center, and Department of Medicine, Joan and Sanford Weill Medical College of Cornell University, 1275 York Avenue, 10021 New York, NY, USA
Abstract In the past, the treatment options for patients with metastatic prostate cancer that progressed despite castrate levels of testosterone was limited, and no therapies provided an improvement in survival. The majority of these patients had extensive osseous disease, multiple comorbidities, and poor performance status. With the widespread use of prostate-specific antigen (PSA) to monitor their clinical course, patients have presented with less extensive disease and a better performance status. Clinical trial methodology has improved as well, through incorporation of post-therapy changes in PSA to evaluate novel agents. This approach allows more patients to enter clinical trials, and the results show that the majority of these patients will have significant reduction in pain, regression of measurable disease, and suppression of PSA. These data suggest that prostate cancer is not as resistant to chemotherapy as it was once thought to be.
Screening Preferences of Patients at Familial Risk of Colorectal Cancer
Paul C. Schroy III1, 3 , Julie T. Glick1, Patricia A. Robinson1 and Timothy Heeren2
(1) Department of Medicine, Boston University School of Medicine, Boston, MA, USA
(2) Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA
(3) Boston Medican Center, 85 East Concord Street, Boston, 02118, USA
Received: 4 August 2006 Accepted: 7 November 2006 Published online: 3 April 2007
Abstract Our primary objective was to assess the screening preferences of patients at familial risk of colorectal cancer. Asymptomatic subjects aged 18–75 with a single first-degree relative diagnosed with colorectal cancer (n = 48) or polyps (n = 52) were asked to identify a preferred screening strategy, test features influencing their choice, and level of interest in decision-making after reviewing a decision aid describing the pros and cons of currently recommended screening tests. Although both groups preferred colonoscopy, 40% of subjects with a family history of colorectal cancer and 48% of those with a family history of polyps preferred alternative strategies. Accuracy was the most commonly identified test feature influencing test preference. Most subjects (66%) felt that selection of screening test should be a patient dominant or shared process. We conclude that patients at familial risk of colorectal cancer have distinct screening preferences that often vary from current recommendations.
Keywords Colorectal cancer - Screening - Familial risk - Colonoscopy - Shared decision-making
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(1) Department of Medicine, Boston University School of Medicine, Boston, MA, USA
(2) Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA
(3) Boston Medican Center, 85 East Concord Street, Boston, 02118, USA
Received: 4 August 2006 Accepted: 7 November 2006 Published online: 3 April 2007
Abstract Our primary objective was to assess the screening preferences of patients at familial risk of colorectal cancer. Asymptomatic subjects aged 18–75 with a single first-degree relative diagnosed with colorectal cancer (n = 48) or polyps (n = 52) were asked to identify a preferred screening strategy, test features influencing their choice, and level of interest in decision-making after reviewing a decision aid describing the pros and cons of currently recommended screening tests. Although both groups preferred colonoscopy, 40% of subjects with a family history of colorectal cancer and 48% of those with a family history of polyps preferred alternative strategies. Accuracy was the most commonly identified test feature influencing test preference. Most subjects (66%) felt that selection of screening test should be a patient dominant or shared process. We conclude that patients at familial risk of colorectal cancer have distinct screening preferences that often vary from current recommendations.
Keywords Colorectal cancer - Screening - Familial risk - Colonoscopy - Shared decision-making
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Chemotherapy for advanced prostate cancer: Results of new clinical trials and future studies
Andrew J. Armstrong1 and Michael A. Carducci1
(1) Prostate Cancer Research Program, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, CRB 1M88, 1650 Orleans Street, 21231 Baltimore, MD, USA
Abstract Our understanding of the role of chemotherapy for advanced prostate cancer has improved considerably in 2004 with the publication of two large randomized phase III trials and the approval by the US Food and Drug Administration of docetaxel and prednisone for metastatic hormone-refractory disease. Although treatment is still considered palliative in nature, studies of chemotherapy for metastatic hormone-refractory prostate cancer (HRPC) have demonstrated improved overall survival compared with older regimens as well as clinically significant improvements in important endpoints, such as quality of life and time to progression. In particular, docetaxel has emerged as first-line therapy on an every-3-week schedule for metastatic HRPC, replacing mitoxantrone, as recently reported in the TAX327 trial. Docetaxel and estramustine combinations have the disadvantage of significant cardiovascular and gastrointestinal toxicity, and further use of estramustine is likely unwarranted as first-line therapy. Future trials examining novel biologic agents and combination therapies should use single-agent docetaxel as the reference standard. The role of chemotherapy for advanced disease in the neoadjuvant or adjuvant setting, in biochemically (PSA) relapsed patients, and as second-line therapy for relapsed disease, remains a subject of active clinical investigation.
(1) Prostate Cancer Research Program, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, CRB 1M88, 1650 Orleans Street, 21231 Baltimore, MD, USA
Abstract Our understanding of the role of chemotherapy for advanced prostate cancer has improved considerably in 2004 with the publication of two large randomized phase III trials and the approval by the US Food and Drug Administration of docetaxel and prednisone for metastatic hormone-refractory disease. Although treatment is still considered palliative in nature, studies of chemotherapy for metastatic hormone-refractory prostate cancer (HRPC) have demonstrated improved overall survival compared with older regimens as well as clinically significant improvements in important endpoints, such as quality of life and time to progression. In particular, docetaxel has emerged as first-line therapy on an every-3-week schedule for metastatic HRPC, replacing mitoxantrone, as recently reported in the TAX327 trial. Docetaxel and estramustine combinations have the disadvantage of significant cardiovascular and gastrointestinal toxicity, and further use of estramustine is likely unwarranted as first-line therapy. Future trials examining novel biologic agents and combination therapies should use single-agent docetaxel as the reference standard. The role of chemotherapy for advanced disease in the neoadjuvant or adjuvant setting, in biochemically (PSA) relapsed patients, and as second-line therapy for relapsed disease, remains a subject of active clinical investigation.
Metastectomy for combined hepatic and extrahepatic colorectal cancer metastases
Karen A. Beaty and Steven A. Curley1
(1) Department of Surgical Oncology, The University of Texas, M.D. Anderson Cancer Center, 1400 Holcombe Boulevard, Unit 444, Houston, TX 77030, USA
Published online: 30 May 2007
Abstract The role of resection of hepatic colorectal cancer metastases is generally accepted. The presence of extrahepatic metastatic disease came to be considered an absolute contraindication to resection of hepatic colorectal cancer metastases in the late 1980s and early 1990s. This dogmatic surgical view developed at a time when there were few active systemic chemotherapeutic options available to treat patients with stage IV colorectal cancer. Recent studies have indicated that complete surgical resection of all hepatic and extrahepatic metastatic disease can yield 5-year overall survival rates in excess of 30% in carefully selected patients. Response to chemotherapy may be an important prognostic indicator in patients with combined hepatic and extrahepatic metastatic disease. The presence of extrahepatic disease should no longer be considered an absolute contraindication to surgical treatment, and multidisciplinary treatment planning should be considered in all patients with potentially resectable hepatic and extrahepatic colorectal cancer metastases.
(1) Department of Surgical Oncology, The University of Texas, M.D. Anderson Cancer Center, 1400 Holcombe Boulevard, Unit 444, Houston, TX 77030, USA
Published online: 30 May 2007
Abstract The role of resection of hepatic colorectal cancer metastases is generally accepted. The presence of extrahepatic metastatic disease came to be considered an absolute contraindication to resection of hepatic colorectal cancer metastases in the late 1980s and early 1990s. This dogmatic surgical view developed at a time when there were few active systemic chemotherapeutic options available to treat patients with stage IV colorectal cancer. Recent studies have indicated that complete surgical resection of all hepatic and extrahepatic metastatic disease can yield 5-year overall survival rates in excess of 30% in carefully selected patients. Response to chemotherapy may be an important prognostic indicator in patients with combined hepatic and extrahepatic metastatic disease. The presence of extrahepatic disease should no longer be considered an absolute contraindication to surgical treatment, and multidisciplinary treatment planning should be considered in all patients with potentially resectable hepatic and extrahepatic colorectal cancer metastases.
Adjuvant therapy for colon cancer
Jeffrey Cilley and Mary F. Mulcahy1
(1) Division of Hematology/Oncology, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, 676 North Saint Clair, Suite 850, 60611 Chicago, IL, USA
Abstract Colon cancer is a leading cause of cancer and cancer deaths in Western countries. Although 5-fluorouracil is still the basis of adjuvant therapy, advances in drug development have led to increased efficacy with the addition of oxaliplatin and options for oral therapy with capecitabine. The benefit of adjuvant therapy for stage II disease is consistently small and not statistically signifi-cant. Future studies will evaluate the role of the biologic agents that have proved to be effective in metastatic disease and better delineate the population at risk by identifying prognostic and predictive markers.
(1) Division of Hematology/Oncology, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, 676 North Saint Clair, Suite 850, 60611 Chicago, IL, USA
Abstract Colon cancer is a leading cause of cancer and cancer deaths in Western countries. Although 5-fluorouracil is still the basis of adjuvant therapy, advances in drug development have led to increased efficacy with the addition of oxaliplatin and options for oral therapy with capecitabine. The benefit of adjuvant therapy for stage II disease is consistently small and not statistically signifi-cant. Future studies will evaluate the role of the biologic agents that have proved to be effective in metastatic disease and better delineate the population at risk by identifying prognostic and predictive markers.
Evaluation on quality of life for gynecologic cancer patients
Guo Yi 1 , Sheng Xiu-jie 1, Liu Yang 2 and Hua Xiang-feng 3
(1) Department of Gynecology, The First Hospital, China Medical University, 110001 Shengyang
(2) Department of Gynecology, Shenbei Hospital of Shenyang Railway Bureau, 110032 Shengyang
(3) Department of Obstetric and Gynecology, People’s Hospital of Liaoning Province, 110016 Shenyang
Received: 21 May 2004 Accepted: 24 September 2004
Abstract Objective: To compare the quality of life (QOL) for gynecologic cancer patients with different cancer sites and to assess the impact of patients’ characteristics, disease parameters, and treatments on the subscale and overall QOL. Methods: A prospective study was conducted including 146 gynecologic cancer patients. QOL data were collected using the general Functional Assessment of Cancer Therapy (FACT- G) QOL questionnaire. Results: Advanced stage patients showed significantly poor physical well-being, emotional well-being, and functional well-being, as compared with early stage patients. QOL was reported higher in older patients (P=0.03), patients above high school education (P=0.004), and patients with help at home (P=0.009). Conclusion: Patients with later stage, multi- modality therapy, poor education, and little social support have the most significant impairments and need more support.
Key words Quality of life - Gynecologic cancer - Patient questionnaire
CLC number R737.3
Biography: GUO Yi(1966–), male, doctor of medicine associate professor, China Medical University, majors in gynecology.
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(1) Department of Gynecology, The First Hospital, China Medical University, 110001 Shengyang
(2) Department of Gynecology, Shenbei Hospital of Shenyang Railway Bureau, 110032 Shengyang
(3) Department of Obstetric and Gynecology, People’s Hospital of Liaoning Province, 110016 Shenyang
Received: 21 May 2004 Accepted: 24 September 2004
Abstract Objective: To compare the quality of life (QOL) for gynecologic cancer patients with different cancer sites and to assess the impact of patients’ characteristics, disease parameters, and treatments on the subscale and overall QOL. Methods: A prospective study was conducted including 146 gynecologic cancer patients. QOL data were collected using the general Functional Assessment of Cancer Therapy (FACT- G) QOL questionnaire. Results: Advanced stage patients showed significantly poor physical well-being, emotional well-being, and functional well-being, as compared with early stage patients. QOL was reported higher in older patients (P=0.03), patients above high school education (P=0.004), and patients with help at home (P=0.009). Conclusion: Patients with later stage, multi- modality therapy, poor education, and little social support have the most significant impairments and need more support.
Key words Quality of life - Gynecologic cancer - Patient questionnaire
CLC number R737.3
Biography: GUO Yi(1966–), male, doctor of medicine associate professor, China Medical University, majors in gynecology.
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Chemotherapy for advanced pancreatic cancer: Past, present, and future
Gregory Friberg1 and Hedy Lee Kindler1
(1) Section of Hematology/Oncology, University of Chicago, 5841 S. Maryland Avenue, MC 2115, 60637-1470 Chicago, IL, USA
Abstract Advanced pancreatic cancer is a devastating illness characterized by significant morbidity and a brief median survival. Although standard chemotherapy with gemcitabine achieves only modest improvements in survival and quality of life, classic cytotoxic agents, such as 5-fluorouracil, pemetrexed, irinotecan, exatecan, cisplatin, or oxaliplatin, given alone or in combination with gemcitabine, have not proved superior. Thus, more recent trials have focused on targeting the biologic characteristics of pancreatic cancer. Although phase III trials of farnesyl transferase and matrix metalloproteinase inhibitors have not improved survival, encouraging preliminary results have been observed in phase II studies of inhibitors of the vascular endothelial growth factor and the epidermal growth factor receptor.
(1) Section of Hematology/Oncology, University of Chicago, 5841 S. Maryland Avenue, MC 2115, 60637-1470 Chicago, IL, USA
Abstract Advanced pancreatic cancer is a devastating illness characterized by significant morbidity and a brief median survival. Although standard chemotherapy with gemcitabine achieves only modest improvements in survival and quality of life, classic cytotoxic agents, such as 5-fluorouracil, pemetrexed, irinotecan, exatecan, cisplatin, or oxaliplatin, given alone or in combination with gemcitabine, have not proved superior. Thus, more recent trials have focused on targeting the biologic characteristics of pancreatic cancer. Although phase III trials of farnesyl transferase and matrix metalloproteinase inhibitors have not improved survival, encouraging preliminary results have been observed in phase II studies of inhibitors of the vascular endothelial growth factor and the epidermal growth factor receptor.
Adjuvant therapy approaches to breast cancer: Should taxanes be incorporated?
Edith A. Perez1
(1) Division of Hematology and Oncology, Mayo Clinic Jacksonville, 4500 San Pablo Road, 32224 Jacksonville, FL, USA
Abstract The triplet of docetaxel, doxorubicin, and cyclophosphamide (TAC) has emerged as an alternative chemotherapy regimen for adjuvant management of node-positive breast cancer. Based on recently reported 3-year data from the Breast Cancer International Research Group (BCIRG) 001, disease-free survival was significantly higher in patients who underwent adjuvant chemotherapy with TAC rather than the established regimen of 5-fluorouracil, doxorubicin, and cyclophosphamide (FAC). TAC reduced the risk of disease recurrence in estrogen receptor-positive and -negative patients. Whereas overall survival was not significantly different between the two groups, TAC led to a significant reduction in mortality in the subset of patients with one to three involved axillary lymph nodes. Overall, these interim BCIRG 001 results, coupled with those from Cancer and Leukemia Group B-9344 and National Surgical Adjuvant Breast and Bowel Project (NSABP) B-28 (phase III trials of sequential adjuvant chemotherapy with doxorubicin and cyclophosphamide followed by paclitaxel), suggest that taxanes are a valuable component of adjuvant chemotherapy for patients with node-positive breast cancer, including those with estrogen receptor positivity and/or extensive lymph node involvement. Accumulating data in the neoadjuvant setting lend further support to the view that the taxanes confer clinically meaningful benefits in the management of early-stage breast cancer. Such ongoing studies as NSABP B-30 will be instrumental in establishing the relative merits of sequential versus concurrent taxane-anthracycline adjuvant regimens for patients with node-positive breast cancer.
(1) Division of Hematology and Oncology, Mayo Clinic Jacksonville, 4500 San Pablo Road, 32224 Jacksonville, FL, USA
Abstract The triplet of docetaxel, doxorubicin, and cyclophosphamide (TAC) has emerged as an alternative chemotherapy regimen for adjuvant management of node-positive breast cancer. Based on recently reported 3-year data from the Breast Cancer International Research Group (BCIRG) 001, disease-free survival was significantly higher in patients who underwent adjuvant chemotherapy with TAC rather than the established regimen of 5-fluorouracil, doxorubicin, and cyclophosphamide (FAC). TAC reduced the risk of disease recurrence in estrogen receptor-positive and -negative patients. Whereas overall survival was not significantly different between the two groups, TAC led to a significant reduction in mortality in the subset of patients with one to three involved axillary lymph nodes. Overall, these interim BCIRG 001 results, coupled with those from Cancer and Leukemia Group B-9344 and National Surgical Adjuvant Breast and Bowel Project (NSABP) B-28 (phase III trials of sequential adjuvant chemotherapy with doxorubicin and cyclophosphamide followed by paclitaxel), suggest that taxanes are a valuable component of adjuvant chemotherapy for patients with node-positive breast cancer, including those with estrogen receptor positivity and/or extensive lymph node involvement. Accumulating data in the neoadjuvant setting lend further support to the view that the taxanes confer clinically meaningful benefits in the management of early-stage breast cancer. Such ongoing studies as NSABP B-30 will be instrumental in establishing the relative merits of sequential versus concurrent taxane-anthracycline adjuvant regimens for patients with node-positive breast cancer.
Long-term survival after radical resection of advanced pancreatic cancer
Motoki Abe1 , Satoshi Kondo1, Satoshi Hirano1, Yoshiyasu Ambo1, Eiichi Tanaka1, Toshiaki Morikawa1, Shunichi Okushiba1 and Hiroyuki Katoh1
(1) Department of Surgical Oncology, Division of Cancer Medicine, Hokkaido University Graduate School of Medicine, Kita-15, Nishi-7, Kita-Ku, 060-8638 Sapporo, Japan
Abstract A 65-yr-old man who underwent pancreaticoduodenectomy with portal vein resection for pancreatic cancer is alive 8 yr after surgery. Originally, computed tomography (CT) revealed an 8-cm tumor in the pancreatic head. The tumor had infiltrated the portal vein, but grew expansively, so there was neither biliary obstruction nor jaundice. Pancreaticoduodenectomy with resection of the portal vein was performed for pancreatic cancer. Many tumor-infiltrating lymphocytes were seen within cancer cell nests on routine histopathology. We performed immunostaining for CD8, and found that a large number of the lymphocytes were CD8+ T cells. The patient’s prognosis was considered poor because the tumor was large and had infiltrated the portal vein. We suspect that long-term survival may be related to the response of CD8+ T cells to the cancer.
Key Words Pancreatic cancer - CD8+ - tumor-infiltrating lymphocyte - prognosis
(1) Department of Surgical Oncology, Division of Cancer Medicine, Hokkaido University Graduate School of Medicine, Kita-15, Nishi-7, Kita-Ku, 060-8638 Sapporo, Japan
Abstract A 65-yr-old man who underwent pancreaticoduodenectomy with portal vein resection for pancreatic cancer is alive 8 yr after surgery. Originally, computed tomography (CT) revealed an 8-cm tumor in the pancreatic head. The tumor had infiltrated the portal vein, but grew expansively, so there was neither biliary obstruction nor jaundice. Pancreaticoduodenectomy with resection of the portal vein was performed for pancreatic cancer. Many tumor-infiltrating lymphocytes were seen within cancer cell nests on routine histopathology. We performed immunostaining for CD8, and found that a large number of the lymphocytes were CD8+ T cells. The patient’s prognosis was considered poor because the tumor was large and had infiltrated the portal vein. We suspect that long-term survival may be related to the response of CD8+ T cells to the cancer.
Key Words Pancreatic cancer - CD8+ - tumor-infiltrating lymphocyte - prognosis
Adjuvant systemic therapy of early stage breast cancer
William J. Gradishar1
(1) Division of Hematology/Oncology, The Feinberg School of Medicine, Northwestern University, 676 North St. Clair Street, Suite 850, 60611 Chicago, IL, USA
Opinion statement Adjuvant chemotherapy reduces the risk of recurrence and mortality in patients with early stage breast cancer. Anthracycline-based regimens are the most widely used standard in the United States. The inclusion of the taxanes into adjuvant chemotherapy programs offers an improvement in disease-free survival rates and probably overall survival rates compared to an anthracycline-based regimen alone. Although adjuvant chemotherapy is effective in all age groups, the magnitude of benefit is greatest in younger premenopausal patients. Treatment decisions need to be individualized. Dose-dense chemotherapy approaches are promising and can be considered an option for patients with early stage breast cancer. Adjuvant tamoxifen therapy should be administered for 5 years in patients with hormone receptor-positive breast cancer. Adjuvant tamoxifen should be administered after the completion of adjuvant chemotherapy. Data from the ATAC (Arimidex, tamoxifen, alone, or in combination) trial provide a compelling argument for choosing anastrozole as adjuvant endocrine therapy in postmenopausal women with hormone receptor-positive early stage breast cancer. Long-term follow-up of patients is necessary to determine the effects of chronic aromatase inhibitor treatment on bone density, cognitive function, and other endpoints.
(1) Division of Hematology/Oncology, The Feinberg School of Medicine, Northwestern University, 676 North St. Clair Street, Suite 850, 60611 Chicago, IL, USA
Opinion statement Adjuvant chemotherapy reduces the risk of recurrence and mortality in patients with early stage breast cancer. Anthracycline-based regimens are the most widely used standard in the United States. The inclusion of the taxanes into adjuvant chemotherapy programs offers an improvement in disease-free survival rates and probably overall survival rates compared to an anthracycline-based regimen alone. Although adjuvant chemotherapy is effective in all age groups, the magnitude of benefit is greatest in younger premenopausal patients. Treatment decisions need to be individualized. Dose-dense chemotherapy approaches are promising and can be considered an option for patients with early stage breast cancer. Adjuvant tamoxifen therapy should be administered for 5 years in patients with hormone receptor-positive breast cancer. Adjuvant tamoxifen should be administered after the completion of adjuvant chemotherapy. Data from the ATAC (Arimidex, tamoxifen, alone, or in combination) trial provide a compelling argument for choosing anastrozole as adjuvant endocrine therapy in postmenopausal women with hormone receptor-positive early stage breast cancer. Long-term follow-up of patients is necessary to determine the effects of chronic aromatase inhibitor treatment on bone density, cognitive function, and other endpoints.
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