Influence of treatment schedule on toxicity and efficacy of cyclophosphamide, epirubicin, and fluorouracil in metastatic breast cancer: a randomized trial comparing weekly and every-4-week administration.

PURPOSE: To compare the effect on toxicity and efficacy of the fluorouracil 500 mg/m2, epirubicin 60 mg/m2, and cyclophosphamide 500 mg/m2 (FEC) regimen divided into 4 weekly doses with conventional every-4-week administration in metastatic breast cancer. PATIENTS AND METHODS: The inclusion criteria demanded measurable or assessable metastases from breast cancer and a World Health Organization (WHO) performance index of 2 or less. One hundred seventy-three patients with metastatic breast cancer who had not been treated with anthracyclines were randomized to receive FEC once every 4 weeks or once a week. The scheduled monthly doses of the cytotoxic agents were identical in both groups. Three patients were excluded from analysis. RESULTS: Hematologic toxicity, alopecia, nausea, and vomiting were significantly more severe in the group that received treatment every 4 weeks. The response rate was higher in the group that received FEC every 4 weeks than in the group treated weekly (47% v 30%, P = .02). Time to progression was significantly (P = .005) longer with every-4-week FEC treatment (median, 9.2 months v 5.4 months for weekly treatment). Patients in the group treated every 4 weeks lived significantly (P = .01) longer than patients treated weekly (median survival times, 21.2 months v 11.8 months, respectively). The actually delivered monthly dose levels and treatment duration were similar in the two groups. CONCLUSION: Both efficacy and toxicity of FEC were greater when treatment was administered every 4 weeks rather than once a week, despite identical dose intensity.