ADJUVANT TREATMENT OF NODE-POSITIVE BREAST-CANCER WITH CYCLOPHOSPHAMIDE, DOXORUBICIN, FLUOROURACIL AND VINCRISTINE VERSUS CYCLOPHOSPHAMIDE,METHOTREXATE, AND FLUOROURACIL - FINAL REPORT AFTER A 16-YEAR MEDIAN FOLLOW-UP DURATION

Purpose: To determine the long-term impact on disease-free survival (D FS) and overall survival (OS) of adjuvant anthracycline-based chemothe rapy, when prospectively compared by random allocation with standard c yclophosphamide, methotrexate, and fluorouracil (CMF) in node-positive (N+) breast cancer patients. Patients and Methods: Two hundred forty- nine patients with N+ breast cancer, recruited from eight French cance r centers, were randomized to receive 12 monthly cycles of adjuvant ch emotherapy, either CMF (n = 112) or doxorubicin, vincristine, cyclopho sphamide, and fluorouracil (AVCF) (n = 136). All had a negative metast atic work-up before inclusion, which was stratified by accrual center, tumor stage (international Union Against Cancer [UICC]), and menopaus al status. Results: No severe adverse effect related to grade 4 (World Health Organization [WHO]) toxicity was observed. There was no differ ence in second primary tumor incidence between the two arms. The treat ment given was 88% of planned for AVCF and 75% for CMF in both premeno pausal and menopausal patients. With a median follow-up time of 16 yea rs (range, 13 to 17), the OS and DFS rates ore significantly longer in the AVCF arm (56% v 41% [P = .01] for OS, and 53% v 36% [P = .006] fo r DFS). These differences ore significant, Irrespective of tumor stage (T1 to T2 v T3 to T4), and remain positive in patients with or withou t postoperative locoregional radiotherapy (55% of cohort). When analyz ed according to menopausal status, the differences remain significant only for premenopausal patients. Conclusion: This set of mature contro lled data confirms the added value of anthracycline-based combination adjuvant chemotherapy for N+ breast cancer patients when compared with CMF, with both regimens given for 1 year. (C) 1996 by American Societ y of Clinical Oncology.