ADJUVANT CYCLOPHOSPHAMIDE, METHOTREXATE, AND FLUOROURACIL VERSUS FLUOROURACIL, EPIRUBICIN, AND CYCLOPHOSPHAMIDE CHEMOTHERAPY IN PREMENOPAUSAL WOMEN WITH AXILLARY NODE-POSITIVE OPERABLE BREAST-CANCER - RESULTS OF A RANDOMIZED TRIAL

Purpose: To determine whether a combination chemotherapy regimen that contains epirubicin (fluorouracil, epirubicin, and cyclophosphamide [F EC]) is superior to the standard cyclophosphamide, methotrexate, and f luorouracil (CMF) combination in premenopausal women with axillary nod e-positive operable breast cancer. Patients and Methods: The Internati onal Collaborative Cancer Group (ICCG) conducted a large randomized tr ial in which two alternative schedules were used according to particip ating center: CMF1 versus FECI and CMF2 versus FEC2 Results: Seven hun dred fifty-nine patients were entered onto the trial. At a median foll ow-up time of 4.5 years, no significant benefit for the anthracycline- containing regimen was observed in terms of relapse-free (P = .61) or overall survival (P = .13). FEC1 and CMF1 appear to be of similar effi cacy, but there is a suggestion that FEC2 may be superior to CMF2, sin ce patients who received FEC2 had improved overall (P = .02) and relap se-free survival (P = .03) rates. Nausea and vomiting and alopecia wer e more common in the epirubicin:containing regimen (P = .001). Conclus ion: We conclude that the FEC2 regimen, in which epirubicin replaced t he methotrexate in CMF, is the preferable adjuvant chemotherapy regime n for premenopausal patients with operable axillary node-positive brea st cancer.