CMF (cyclophosphamide, methotrexate, 5-fluorouracil) versus CNF (cyclophosphamide, mitoxantrone, 5-fluorouracil) as adjuvant chemotherapy for stage II lymph-node positive breast cancer - A phase III randomized multicenter study

A multicenter phase III randomized study compared the efficacies of two adj uvant polychemotherapeutic regimens in 145 patients with stage H node-posit ive breast cancer. The standard chemotherapy combination, CMF (cyclophospha mide, methotrexate, 5-fluorouracil), was administered to 77 women. The expe rimental protocol, CNF (cyclophosphamide, mitoxantrone, 5-FU), in which mit oxantrone (Novantrone) replaced methotrexate, was given to 68 patients. Fol low-up of the 145 patients by six participating hospitals showed no statist ically significant difference (p = 0.6) between the two treatment regimens during a median follow-up of 4.5 years in terms of overall survival. There was, however, a significant advantage (p = 0.04) in the disease-free surviv al for those receiving mitoxantrone (mean survival 4.4 years for CNF versus 2.7 years for CMF). Toxic side effects associated with CNF (particularly a lopecia and myelotoxicity) were relatively more frequent but acceptable and did not lead to dose reduction. In light of its association with improved disease-free survival in this study, larger studies should be undertaken on the role of mitoxantrone as adjuvant treatment in stage Il breast cancer.