Phase I trial of the novel taxane BMS-184476 administered in combination with carboplatin every 21 days.
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| Abstract |
The aim of the study was to determine the maximum-tolerated dose and dose-limiting toxicities for BMS-184476, in combination with carboplatin, in patients with advanced solid tumours and to describe any preliminary antitumour activity associated with this regimen. Patients received combination therapy with BMS-184476 given intravenously over 1 h followed by carboplatin administered over 30 min on day 1 of a 21-day cycle. In all, 28 patients received 146 cycles of BMS-184476 and carboplatin. Patients were enrolled at four dose levels: BMS-184476 (mg m(-2))/carboplatin (mg min ml(-1)): 40/5, 50/5, 50/6 and 60/6. Dose-limiting toxicity at 60/6 was neutropenia. Among 27 evaluable patients, 11 demonstrated stable disease for a median of 8.5 cycles. In 22 patients, the pharmacokinetics of BMS-184476 appeared independent of dose of BMS-184476. The mean+/-s.e.m. values for clearance (Cl), volume of distribution at steady state and apparent terminal half-life of BMS-184476 in the four dose groups during cycle 1 were 192+/-25 ml min m(-2), 377+/-69 l m(-2) and 33.7+/-5.9 h, respectively. An increase in the dose of carboplatin from 5 to 6 mg min ml(-1) may have decreased Cl of BMS-184476. BMS-184476 in combination with carboplatin was well tolerated at a dose of 50/6 and shows evidence of antitumour activity in a pretreated population.
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| Authors | J H Bilenker, J P Stevenson, M L Gallagher, D Vaughn, M B Cohen, P J O'Dwyer |
| Journal | British journal of cancer (Br J Cancer) Vol. 91 Issue 2 Pg. 213-8 (Jul 19 2004) ISSN: 0007-0920 [Print] England |
| PMID | 15213727 (Publication Type: Clinical Trial, Clinical Trial, Phase I, Journal Article, Research Support, Non-U.S. Gov't) |
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