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Cancer Chemotherapy and Pharmacology
Published in: Cancer Chemotherapy and Pharmacology 5/2004

01-05-2004 | Original Article

A phase I, dose escalation trial of ZD0473, a novel platinum analogue, in combination with gemcitabine

Authors: Keith T. Flaherty, James P. Stevenson, Maryann Redlinger, Kenneth M. Algazy, Bruce Giantonio, Peter J. O’Dwyer

Published in: Cancer Chemotherapy and Pharmacology | Issue 5/2004

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Abstract

Purpose

To develop a combination regimen for clinical testing, we performed a dose escalation study of ZD0473 in combination with gemcitabine. ZD0473 is a novel platinum analogue with an aliphatic cyclic carrier ligand. In vitro and in vivo studies suggest that it possesses a different spectrum of antitumor activity from cisplatin and carboplatin. In single-agent studies of ZD0473, myelosuppression was the predominant toxicity and responses were observed.

Methods

In this combination phase I trial, 36 patients with advanced cancer were accrued to four dose levels, with doses of ZD0473 and gemcitabine ranging from 60 to 120 mg/m2 and 600 to 750 mg/m2, respectively. ZD0473 was administered on day 1 and gemcitabine was given on days 1 and 8 of a 21-day cycle.

Results

Hematologic toxicity was dose-limiting. Grade 3 and 4 thrombocytopenia and neutropenia occurred during 60% and 41% of all cycles. Nonhematologic toxicities were mild and reversible. Two partial responses and 19 patients with stable disease were observed.

Conclusions

The recommended phase II doses are 90 mg/m2 of ZD0473 and 750 mg/m2 of gemcitabine for lightly pretreated patients and 600 mg/m2 for heavily pretreated patients. The combination of ZD0473 and gemcitabine is associated with dose-dependent thrombocytopenia and neutropenia as well as having promising clinical activity.
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Metadata
Title
A phase I, dose escalation trial of ZD0473, a novel platinum analogue, in combination with gemcitabine
Authors
Keith T. Flaherty
James P. Stevenson
Maryann Redlinger
Kenneth M. Algazy
Bruce Giantonio
Peter J. O’Dwyer
Publication date
01-05-2004
Publisher
Springer-Verlag
Published in
Cancer Chemotherapy and Pharmacology / Issue 5/2004
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI
https://doi.org/10.1007/s00280-003-0754-1

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