A controlled trial of adjuvant chemotherapy with melphalan versus cyclophosphamide, methotrexate, and fluorouracil for breast cancer

The hypothesis that chemotherapy may be more effective when there is only a slight tumor burden has led to its use after mastectomy in patients at high risk of recurrence. The preliminary results of a trial of melphalan (l-PAM) as adjuvant therapy carried out by the National Surgical Adjuvant Breast Project (NSABP) [1], suggested that melphalan therapy could significantly prolong postoperative relapse-free survival (RFS). Because of the importance of these findings we decided, in March 1975, to repeat the trial at the breast unit at Guy’s Hospital. Results from the Istituto Nationale Tumori in Milan on the use of a combination of cyclophosphamide, methotrexate, and fluorouracil (CMF) in patients with involved axillary nodes after mastectomy [2] suggested that postoperative RFS could be prolonged by chemotherapy. These findings led to the establishment, in March 1976, of a three-armed trial in the University Hospital of South Manchester comparing no adjuvant treatment, melphalan, and CMF. Because of the similarity of protocols and interests at Guy’s Hospital and in Manchester, we decided in 1979 to amalgamate the trials. We now report the results of the combined randomised trial comparing adjuvant melphalan, adjuvant CMF, and no adjuvant therapy.