PHASE-II TRIAL OF DOCETAXEL - A NEW, HIGHLY EFFECTIVE ANTINEOPLASTIC AGENT IN THE MANAGEMENT OF PATIENTS WITH ANTHRACYCLINE-RESISTANT METASTATIC BREAST-CANCER

Purpose: To determine the efficacy (objective response rate and durati on of response and survival) and toxicity of docetaxel in patients wit h strictly defined anthracycline-resistont metastatic breast cancer (M BC). Patients and Methods: Thirty-five patients with bidimensionally m easurable MBC who had progressive disease while receiving anthracyclin e-containing chemotherapy were registered onto the phase II trial, Doc etaxel wets administered at a dose of 100 mg/m(2) over 1 hour every 21 days. Results: Thirty-four patients were assessable for disease respo nse; 18 (53%; 95% confidence interval [CI], 35% to 70%) achieved a par tial response, The median times to disease progression and survival du ration were 7.5 and 13.5 months, respectively, for responding patients . The median overall survival duration was 9 months, Two hundred eight cycles (median, five) of docetaxel were administered. Neutropenia wit h less than 500 cells/mu L developed in 31 of 35 patients; it was comp licated by fever in 30 (14%) of 208 cycles and in 18 (51%) of 35 patie nts, including one treatment-related death, Fluid retention was seen i n 15 (43%) of 35 patients, including pleural effusions in 11 patients (31%). Moderate skin toxicity, asthenia, and myalgia were observed in 16%, 58%, and 37% of cycles, respectively. Conclusion: Docetaxel has t he highest reported anti-tumor activity in anthracycline-resistant MBC . High objective response rates were seen in patients with visceral-do minant involvement, multiple metastatic sites, or extensive previous t herapy, Docetaxel is associated with severe bur reversible neutropenia , asthenia, and cumulative dose-related fluid retention. Dexamethasone decreased the frequency and severity of skin toxicity and appeared to ameliorate fluid retention. (C) 1995 by American Society of Clinical Oncology.