PHASE-II TRIAL OF PACLITAXEL BY 3-HOUR INFUSION AS INITIAL AND SALVAGE CHEMOTHERAPY FOR METASTATIC BREAST-CANCER

Purpose: To evaluate the efficacy and safety of paclitaxel administered by 3-hour infusion as initial and salvage chemotherapy for metastatic breast cancer. Patients and Methods: Forty-nine patients with metastatic breast cancer received paclitaxel via 3-hour intravenous infusion after standard premedication. Prophylactic granulocyte colony-stimulating factor (G-CSF) was as nor used, and chemotherapy was cycled every 3 weeks. For 25 patients who received paclitaxel as initial therapy (group I), the starting dose was 250 mg/m(2). Twenty-four patients who had received two or more prior regimens, including an anthracycline (group II), started at 175 mg/m(2). Paclitaxel pharmacokinetics were evaluated in 23 patients in group I. Results: Grade 3 and 4 toxicities included (groups I/II) neutropenia (36%/33%), thrombocytopenia (0%/8%), anemia (0%/13%), neuropathy (8%/0%), arthralgia/myalgia (16%/4%), and mucositis (4%/4%). No significant hypersensitivity-type reactions or cardiac arrhythmias were seen. Six patients who received paclitaxel at greater than or equal to 250 mg/m(2) experienced transient photopsia, without apparent chronic neuro-ophthalmologic sequelae. The mean peak plasma paclitaxel concentration was 5.87 mu mol/L (range, 1.99 to 7.89) for these patients, and 6.08 mu mol/L (range, 0.81 to 13.81) for 17 of 19 patients who did not experience visual symptoms. In 25 assessable patients in group I at a median follow-up time of 12 months, one complete response (CR) and seven partial responses (PRs) have been observed, for a total response rate of 32% (95% confidence interval [CI], 15% to 53%). In group II, five PRs were noted in 24 assessable patients (20.8%; 95% CI, 7% to 42%). Median response durations were 7 months for group I and 4 months for group II. Conclusion: Paclitaxel via 3-hour infusion, without prophylactic G-CSF, is active and safe as initial and subsequent therapy for metastatic breast cancer. The transient visual symptoms noted at higher doses seem unrelated to peak plasma paclitaxel concentration. Further studies that compare 3- and 24-hour (or other) infusion schedules are necessary to determine the optimal administration of paclitaxel in metastatic breast cancer. (C) 1995 by American Society of Clinical Oncology.