Paclitaxel (Taxol): phase I/II trial comparing 1-hour infusion schedules

This phase I/II study was done to evaluate the safety and feasibility of two schedules of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) administered by 1-hour infusion in the outpatient setting. Fifty-six patients with advanced, refractory malignancies received one of two paclitaxel schedules by random assignment: 135 mg/m2 given as a single dose over 1 hour or 135 mg/m2 given in divided hourly daily doses for 3 days. All patients were premedicated with dexamethasone, diphenhydramine, and cimetidine. No serious acute hypersensitivity reactions were seen with either schedule of paclitaxel. Other adverse effects were usually mild and easily tolerated. Other than alopecia, which was universal, myelosuppression was the most common severe toxicity. However, grades 3 and 4 leukopenia occurred in only 19% and 2% of treatment courses, respectively. Nine patients required hospitalization for treatment of fever associated with neutropenia. There were no significant differences in toxicity observed when comparing the two paclitaxel regimens. It is too early to adequately assess tumor response, but thus far 11 of 56 patients (20%) had partial or complete response to therapy. Responses were observed in patients with breast, ovarian, and lung cancers. Paclitaxel can be safely given by 1-hour infusion in the outpatient setting, both as a single dose and in divided doses for 3 days. Severe acute hypersensitivity reactions did not occur in 162 courses. Neutropenia was mild in most patients and severe thrombocytopenia was rare. The use of this dose and these schedules of paclitaxel as a component of combination chemotherapy regimens should be possible. Investigation of paclitaxel at 200 mg/m2 given by 1-hour infusion is currently in progress.