Randomized trial comparing adriamycin vincristine (av) cyclophosphamide methotrexate 5-Fluorouracil prednisone (cmfp) hybrid versus av-cmfp monthly alternated in metastatic breast-cancer

UNLABELLED 194 metastatic breast cancer patients with no prior chemotherapy for advanced disease were randomized to one of two alternating schedules, fulfilling the requisites of Goldie and Coldman's hypothesis to evaluate if the earlier alternation of two non-cross resistant regimens is superior in terms of response (R), duration of R (DR), and survival (SV). TREATMENT arm A: Adriamycin (A) 60 mg/m2 IV day (d) 1 and vincristine (V) 1.4 mg/m2 IV d 1 and 8 monthly alternated with cyclophosphamide (C) 100 mg/m2 p.o. d 1-14; methotrexate (M) 30 mg/m2 IV d 1 and 8; 5-fluorouracil (F) 600 mg/m2 IV d 1 and 8 and prednisone (Pr) 40 mg/m2 p.o. d 1-14. Arm B (hybrid): A 60 mg/m2 IV d 1; V 1.4 mg/m2 IV d 1; C 100 mg/m2 p.o. d 8-14; M 30 mg/m2 IV d 8; F 600 mg/m2 IV d 8 and Pr 40 mg/m2 p.o. d 8-14. RESULTS 87 and 89 patients are evaluable for R. Arm A: R= 59% (51/87); median DR= 13 months (m); median SV= 25 m. Arm B: R= 69% (61/89); median DR= 15 m.; median SV= 29 m. Myelosuppression was slightly more marked in arm B. Three patients had toxic-related deaths (arm A: 1; arm B: 2). CONCLUSIONS a trend favoring an earlier alternation and higher dose intensity (DI) was found regarding to R, DR and SV. However, differences were not statistically significant.