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.