A phase II open-label study of DHA-paclitaxel (Taxoprexin) by 2-h intravenous infusion in previously untreated patients with locally advanced or metas

Robert J. Jones1, Robert E. Hawkins2, Martin M. Eatock3, David R. Ferry4, Ferry A. L. M. Eskens5, HansJochen Wilke6 and T. R. Jeffry Evans1

(1) Centre for Oncology and Applied Pharmacology, Beatson Oncology Centre, Western Infirmary, University of Glasgow, Dumbarton Road, Glasgow, G11 6NT, UK
(2) Paterson Institute for Cancer Research, Christie Hospital, Wilmslow Road, Manchester, M20 4BX, UK
(3) Belfast City Hospital, Lisburn Road, Belfast, BT9 7AB, UK
(4) Deanasly Centre, New Cross Hospital, Wolverhampton, WV10 0QP, UK
(5) Department of Medical Oncology, Erasmus University Medical Centre, PO Box 2040, 3000 CA Rotterdam, The Netherlands
(6) Internal Oncology/Hematology, Kliniken-Essen-Mitte, Henricistrasse 92, Essen, 45136, Germany

Received: 19 December 2006 Accepted: 27 March 2007 Published online: 18 April 2007

Abstract
Purpose Combination chemotherapy regimens can improve survival in patients with advanced gastric and oesophageal adenocarcinoma. Docosahexaenoic acid (DHA)-paclitaxel is a novel conjugate formed by the covalent linkage of the fatty acid DHA to paclitaxel and may result in increased tumour exposure to paclitaxel without increased toxicity.
Patients and methods In this single arm, phase II study of DHA-paclitaxel, eligible patients with previously untreated, inoperable locally advanced or metastatic adenocarcinoma of the oesophagus, oesophago-gastric junction or stomach were treated with DHA-paclitaxel (1,100 mg/m2) administered by 2-h intravenous infusion every 21 days.
Results Fifty-four patients were recruited of whom 53 were evaluable for toxicity, and 48 for response. There were five confirmed partial responses (9.4%) by the RECIST criteria. The median duration of response was 87 days (range 49–97 days), the median time to progression was 84 days (95% CI 78–124 days), and median overall survival was 262 days (95% CI 205–357 days). Grade ≥3 neutropaenia occurred in 93% of patients, and febrile neutropaenia in 17% of patients.
Conclusions DHA-paclitaxel has modest activity in patients with oesophago-gastric cancer and with haematological toxicity that is comparable to paclitaxel and docetaxel.
Keywords Adenocarcinoma - DHA-paclitaxel - Oesophagus - Stomach