Paclitaxel administered by 1-hour infusion. Preliminary results of a phase 1/11 trial comparing two schedules

Abstract

Background. Paclitaxel currently is administered by prolonged intravenous infusion because of the occurrence of severe hypersensitivity reactions in patients in early clinical trials. However, intensive premedication probably is more important in eliminating allergic reactions than is the length of infusion. The authors evaluated the feasibility of two paclitaxel schedules using a 1‐hour, outpatient infusion. Methods. Fifty‐six patients with advanced, refractory malignancies were randomized to receive one of two paclitaxel schedules: 135 mg/m² administered as a single dose over 1 hour, or 135 mg/m² administered in divided daily doses for 3 days, each over 1 hour. All patients were premedicated with dexamethasone, diphenhydramine, and cimetidine. Results. No serious hypersensitivity reactions occurred with either schedule of paclitaxel. In addition, other adverse effects were usually mild and easily tolerated. Other than alopecia, which occurred in all patients, myelosuppression was the most common severe toxicity. However, grade 3 leukopenia occurred in only 19% of treatment courses, and grade 4 leukopenia (nadir < 1000/μL) occurred in only 2%. Nine patients required hospitalization for treatment of infection associated with neutropenia. No significant differences in toxicity were observed when the two paclitaxel regimens were compared. Although it is too early to assess the results adequately, preliminary findings showed that thus far 11 of 56 patints (20%) had a partial or complete response to therapy. Responses were observed in patients with breast, ovarian, and lung cancer. Conclusions. Paclitaxel can be safely administered in a 1‐hour infusion in an outpatient setting, either as a single dose or in divided doses for three days. Severe hypersensitivity reactions did not occur in 162 treatment courses, and neutropenia was mild in most patients. Incorporation of this dose and these schedules of paclitaxel into combination chemotherapy regimens should be feasible. An investigation of higher paclitaxel doses given in a 1‐hour infusion is currently in progress.