A dose-finding study of the weekly administration of paclitaxel in patients with advanced solid tumors

The purpose of this study was to determine the dose-limiting toxicities and the maximum-tolerated dose (MTD) of weekly administration of paclitaxel in patients with advanced solid tumors. Twenty-six patients with advanced sol id tumors were treated with escalated doses of paclitaxel (starting dose 70 mg/m(2)/wk with increments of 10 mg/m(2)/wk) for 4 consecutive weeks every 6 weeks. No intrapatient escalation or growth factor support was allowed. The DLT was exceeded at the dose of 120 mg/m(2)/wk, and the dose-limiting e vents were grade IV neutropenia and treatment delay because of incomplete h ematologic recovery. There was no cumulative myelosuppression. Grade IV neu tropenia occurred in four (6%) cycles, and there was one episode of febrile neutropenia. Grade HU fatigue occurred in 19 (73%) patients, resulting in discontinuation of treatment in 2 of them; grade II neurosensory toxicity a nd grade II alopecia occurred in 8 (31%) patients each. The MTD, which is a lso the recommended dose for further phase II studies, was 110 mg/m(2)/wk. Among the 21 patients with bidimensionally measurable disease, 2 (10%) part ial responses were observed, both in patients with heavily pretreated advan ced breast cancer. The weekly administration of paclitaxel for 4 consecutiv e weeks in cycles of 6 weeks is a feasible, safe, and active outpatient reg imen that merits further evaluation in combination with other anticancer ag ents.