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 administere d by 3-hour infusion as initial and salvage chemotherapy for metastati c breast cancer.Patients and Methods: Forty-nine patients with metasta tic breast cancer received paclitaxel via 3-hour intravenous infusion after standard premedication. Prophylactic granulocyte colony-stimulat ing factor (G-CSF) was as nor used, and chemotherapy was cycled every 3 weeks. For 25 patients who received paclitaxel as initial therapy (g roup I), the starting dose was 250 mg/m(2). Twenty-four patients who h ad received two or more prior regimens, including an anthracycline (gr oup II), started at 175 mg/m(2). Paclitaxel pharmacokinetics were eval uated in 23 patients in group I. Results: Grade 3 and 4 toxicities inc luded (groups I/II) neutropenia (36%/33%), thrombocytopenia (0%/8%), a nemia (0%/13%), neuropathy (8%/0%), arthralgia/myalgia (16%/4%), and m ucositis (4%/4%). No significant hypersensitivity-type reactions or ca rdiac arrhythmias were seen. Six patients who received paclitaxel at g reater than or equal to 250 mg/m(2) experienced transient photopsia, w ithout apparent chronic neuro-ophthalmologic sequelae. The mean peak p lasma 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 o f 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 comp lete response (CR) and seven partial responses (PRs) have been observe d, 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 an d subsequent therapy for metastatic breast cancer. The transient visua l symptoms noted at higher doses seem unrelated to peak plasma paclita xel concentration. Further studies that compare 3- and 24-hour (or oth er) infusion schedules are necessary to determine the optimal administ ration of paclitaxel in metastatic breast cancer. (C) 1995 by American Society of Clinical Oncology.