DOSE-DENSE THERAPY WITH WEEKLY 1-HOUR PACLITAXEL INFUSIONS IN THE TREATMENT OF METASTATIC BREAST-CANCER

Purpose: To evaluate the efficacy and toxicity of paclitaxel administe red as a 1-hour infusion on weekly basis, without interruption, to pat ients with metastatic breast cancer who had received prior therapy. Pa tients and Methods: Thirty patients with metastatic breast cancer rece ived sustained weekly paclitaxel therapy at an initial dose of 100 mg/ m(2) until disease progression. Prior therapy included adjuvant only ( n = 17), metastatic only (n = 7), or both (n = 6). Eighteen patients h ad received prior anthracycline therapy, 12 of whom had demonstrated p rogression of disease within 12 months of it. All patients were assess able for efficacy; 29 patients were assessable for toxicity. Pharmacok inetic studies of paclitaxel were also performed. Results: A total of 469 weekly paclitaxel infusions were administered to 30 patients (medi an, 14 infusions/patient). The median delivered dose-intensity was 91 mg/m(2)/wk (range, 80 to 108). The overall response rate was 53% (95% confidence interval [CI], 34% to 72%), with 10% complete responses (CR s) and 43% partial responses (PRs). Median response duration was 7.5 m onths (range, 2 to 11+). Responses were observed in nine of 18 (50%) p atients with prior anthracycline therapy, including six of 12 (50%) wi th disease progression on anthracycline within 1 year (three of four w ithin 6 months). Therapy was well tolerated and remarkable for a lack of overall and cumulative myelosuppression. Grade 3/4 neutropenia occu rred in four patients; febrile neutropenia was not observed. Periphera l neuropathy prohibited dose escalation above 100 mg/m(2), and grade 3 neuropathy was observed in two of 21 patients at less than or equal t o 100 mg/m(2). Conclusion: Weekly paclitaxel therapy is active and wel l tolerated in patients with metastatic breast cancer. Weekly therapy should be considered as a current clinical option for these patients a nd should be incorporated into future comparative clinical trials. (C) 1998 by American Society of Clinical Oncology.