PHASE-II EVALUATION OF METHOTREXATE, VINBLASTINE, DOXORUBICIN, AND CISPLATIN (M-VAC) IN ADVANCED, MEASURABLE BREAST-CARCINOMA

The purpose of this study was to determine whether methotrexate, vinbl astine, doxorubicin, and cisplatin, each individually active in metast atic breast cancer (MBC), could, in combination, produce an overall re sponse rate, median survival, and long-term survival sufficiently prom ising to merit its consideration for phase III trials in MBC and as in duction therapy prior to autologous bone marrow transplant. From July 1986 through February 1990, 30 patients with stage IV, measurable brea st carcinoma received M-VAC: methotrexate-30 mg/m(2) days 1, 15, 22; v inblastine-3 mg/m(2) days 2, 15, 22; doxorubicin-30 mg/m(2) day 2; cis platin-70 mg/m(2) day 2. Cycles were repeated at 4-week intervals for up to six courses. Median age was 53 years (range 34-64 years). Prior treatment included adjuvant cyclophosphamide, methotrexate, and 5-Fluo rouracil in 12 patients, radiotherapy in 13 patients, and hormonal the rapy in 14 patients. Eleven patients were ER (+) at the time of initia l diagnosis. Five patients had disease restricted to bone and/or nodes ; the other 25 had visceral-dominant sites of metastases, with or with out bone involvement, or evidence of rapid, inflammatory chest wall re lapse. Twenty-nine of 30 patients were evaluable for toxicity and resp onse; all were evaluable for survival. The major overall response rate was 83%, with a 21% complete remission rate. The chief toxicity was b one marrow suppression, with grade 4 granulocytopenia in 20 patients, grade 3 in 7 patients, and grade 3 and 4 thrombocytopenia in 5 patient s. Grade 3 stomatitis occurred in 9 patients. Renal insufficiency was clinically insignificant, and neurotoxicity mild, with 7 patients sust aining grade 1 or 2 paresthesias. Median time to progression was 9 mon ths and median survival 19 months (range, 5-84 + months) with 4 patien ts still alive at least 45 + months or more from the start of treatmen t and 2 presently free of progressive disease. Although highly toxic, M-VAC produces a response rate and survival duration in visceral-domin ant MBC competitive with, if not superior to, conventional regimens su ch as CAF (Cytoxan, doxorubicin, 5-fluorouracil); it therefore merits further investigation in conjunction with hematopoietic growth factors and as cytoreductive therapy prior to autologous bone marrow transpla ntation.