Journal of Clinical Oncology, Vol 9, 2134-2140, Copyright © 1991 by American Society of Clinical Oncology

ARTICLES

Adjuvant chemotherapy with doxorubicin plus cyclophosphamide, methotrexate, and fluorouracil in the treatment of resectable breast cancer with more than three positive axillary nodes

R Buzzoni, G Bonadonna, P Valagussa and M Zambetti
Division of Medical Oncology, Istituto Nazionale Tumori, Milan, Italy.

To improve current adjuvant results in high-risk breast cancer, in February 1982 we activated a prospective randomized trial using both intravenous cyclophosphamide, methotrexate, and fluorouracil (CMF) and Adriamycin (doxorubicin; Farmitalia-Carlo Erba, Milan, Italy) involving patients with resectable mammary carcinoma and more than three positive axillary lymph nodes. The objective of the study was to assess the effectiveness of four courses of Adriamycin followed by eight courses of CMF versus two courses of CMF alternated with one course of Adriamycin for a total of 12 courses. All drug courses were recycled every 3 weeks. Rather than temporarily reducing doses in the event of myelosuppression on the planned day of treatment, drug administration was delayed for 1 to 2 weeks. At a median follow-up of 59 months, treatment outcome was significantly superior for patients who received Adriamycin followed by CMF (Adriamycin----CMF) than for those given alternating regimens (CMF/Adriamycin). The 5-year relapse-free survival was superior post-Adriamycin----CMF (61%) compared with post- CMF/Adriamycin administration (38%; P = .001). The corresponding figures for the 5-year total survival were 78% and 62%, respectively (P = .005). The benefit of Adriamycin----CMF was observed in all patient subsets. Treatment was fairly well tolerated, and we documented only one case of fatal congestive heart failure in a patient who received postoperative irradiation to the left breast in addition to Adriamycin. Present findings indicate that in women with extensive nodal involvement, Adriamycin----CMF yielded superior results compared with CMF/Adriamycin.
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