Dose-dense therapy with weekly 1-hour paclitaxel infusions in the treatment of metastatic breast cancer.

Abstract

PURPOSE To evaluate the efficacy and toxicity of paclitaxel administered as a 1-hour infusion on weekly basis, without interruption, to patients with metastatic breast cancer who had received prior therapy. PATIENTS AND METHODS Thirty patients with metastatic breast cancer received sustained weekly paclitaxel therapy at an initial dose of 100 mg/m2 until disease progression. Prior therapy included adjuvant only (n=17), metastatic only (n=7), or both (n=6). Eighteen patients had received prior anthracycline therapy, 12 of whom had demonstrated progression of disease within 12 months of it. All patients were assessable for efficacy; 29 patients were assessable for toxicity. Pharmacokinetic studies of paclitaxel were also performed. RESULTS A total of 469 weekly paclitaxel infusions were administered to 30 patients (median, 14 infusions/patient). The median delivered dose-intensity was 91 mg/m2/wk (range, 80 to 108). The overall response rate was 53% (95% confidence interval [CI], 34% to 72%), with 10% complete responses (CRs) and 43% partial responses (PRs). Median response duration was 7.5 months (range, 2 to 11+). Responses were observed in nine of 18 (50%) patients with prior anthracycline therapy, including six of 12 (50%) with disease progression on anthracycline within 1 year (three of four within 6 months). Therapy was well tolerated and remarkable for a lack of overall and cumulative myelosuppression. Grade 3/4 neutropenia occurred in four patients; febrile neutropenia was not observed. Peripheral neuropathy prohibited dose escalation above 100 mg/m2, and grade 3 neuropathy was observed in two of 21 patients at < or = 100 mg/m2. CONCLUSION Weekly paclitaxel therapy is active and well tolerated in patients with metastatic breast cancer. Weekly therapy should be considered as a current clinical option for these patients and should be incorporated into future comparative clinical trials.