PHASE-I STUDY OF GEMCITABINE USING A ONCE EVERY 2 WEEKS SCHEDULE

Gemcitabine (2',2'-difluorodeoxycytidine) is a novel nucleoside analog ue, As part of a series of studies to determine the maximum tolerated dose (MTD) of gemcitabine and the most appropriate schedule, a two-cen tre phase I study of gemcitabine was undertaken in patients with advan ced refractory solid tumours using a once every 2 weeks schedule. Fift y-two patients were entered into the study at 14 different dose levels (40-5700 mg m(-2)). Weekly evaluations for toxicity were performed an d the MTD for this once every 2 weeks schedule was 5700 mg m(-2). The dose-limiting toxicity was myelosuppression, with neutropenia being mo st significant, Other toxicities were nausea, vomiting, fever and asth enia. One minor response was seen in a heavily pretreated breast cance r patient treated at 1200 mg m(-2). Preclinical studies suggest that t he efficacy of gemcitabine is more schedule than dose related, and it is concluded that this is not the most appropriate dosing schedule for gemcitabine. However, this study demonstrates the safety profile of g emcitabine, as doses over fourfold greater than that recommended for t he weekly schedule of 1000 mg m(-2) could be tolerated.