Randomized trial of intensive cyclophosphamide, epirubicin, and fluorouracil chemotherapy compared with cyclophosphamide, methotrexate, and fluorouracil in premenopausal women with node-positive breast cancer

Purpose: To determine the relative efficacy of an intensive cyclophasphamide, epirubicin, and fluorouracil (CEF) adjuvant chemotherapy regimen compared with cyclophasphamide, methotrexate, and fluorouracil (CMF) in node-positive breast cancer. Patients and Methods: Premenopausal women with node-positive breast cancer were randomly allocated to receive either cyclophosphamide 100 mg/m(2) orally days 1 through 14; methotrexate 40 mg/m(2) intravenously (IV) days 1 and 8; and fluorouracil 600 mg/m2 IV days 1 and 8 or cyclophosphamide 75 mg/m(2) orally days 1 through 14; epirubicin 60 mg/m(2) IV days 1 and 8; and fluorouracil 500 mg/m(2) IV days 1 and 8. Each cycle was administered monthly for 6 months. Patients administered CEF received antibiotic prophylaxis with cotrimoxazole two tablets twice a day for the duration of chemotherapy. Results: The median follow-up was 59 months. One hundred sixty-nine of the 359 CMF patients developed recurrence compared with 132 of the 351 CEF patients. The corresponding 5-year relapse-free survival rates were 53% and 63%, respectively (P = .009). One hundred seven CMF patients died compared with 85 CEF patients. The corresponding 5-year actuarial survival rates were 70% and 77%, respectively (P = .03). The rate of hospitalization for febrile neutropenia war 1.1% in the CMF group compared with 8.5% in the CEF group. There was one case of congestive heart failure in a patient who received CMF compared with none in the CEF group. Acute leukemia occurred in five patients in the CEF group. Conclusion: The results of this trial show the superiority of CEF over CMF in terms of both disease-free and overall survival in premenopausal women with axillary node-positive breast cancer. J Clin Oncol 16: 2651-2658. (C) 1998 by American Society of Clinical Oncology.