Epirubicin-based chemotherapy in metastatic breast cancer patients: role of dose-intensity and duration of treatment.

PURPOSE: To determine whether the duration and the dose of epirubicin modify the long-term outcome of patients with metastatic breast cancer (MBC). PATIENTS AND METHODS: Four hundred seventeen anthracycline-naive MBC patients were randomized to receive one of the following regimens: arm A: 11 cycles of fluorouracil 500 mg/m(2), epirubicin 75 mg/m(2), and cyclophosphamide 500 mg/m(2) (FEC 75) every 21 days; arm B: four cycles of FEC 100 (same regimen but with epirubicin 100 mg/m(2)) then eight cycles of FEC 50 (epirubicin 50 mg/m(2)); and arm C: four cycles of FEC 100 then restart the same regimen at disease progression in case of prior response or stabilization.
RESULTS: Hematologic toxicity was similar. Nausea/vomiting and stomatitis were significantly less frequent in arm A as was left ventricular ejection fraction decrease in arm C (A = six patients, B = five patients, and C = one patient). Six patients died of infections (A = four patients and C = two patients). After four cycles, the objective response rate (ORR) was better with FEC 100 than with FEC 75 (49.2% v 40%, respectively; P: =.07). The ORR was better with the longer regimens (arm A, 56.9%; B, 64%; and C, 47.6%; P: =.06) and was 41% after second-line FEC 100. After a median follow-up of 41 months, the response duration and time to progression (TTP) were significantly better with arm B, the longer regimen (P: =.012 and P: < 10(-3), respectively). The median survival times for arms A, B, and C were similar (17.9, 18.9, and 16. 3 months, respectively; P: =.49).
CONCLUSION: In MBC, longer epirubicin-based regimens are better in terms of response duration and TTP. FEC 100 regimens improve the ORR. However, four initial cycles of FEC 100 and identical retreatment at disease progression yielded equivalent overall survival to longer regimens.

RCT Entities:   Population Interventions Outcomes