Prospective meta-analysis of randomised trials of cyclophosphamide, methotrexate & fluorouracil (CMF) vs fluorouracil, epirubicin & cyclophosphamide (FEC) chemotherapy in early breast cancer

Abstract

592 Background: Our previous study of node positive (N+) patients (Coombes: JCO 1996 14:35–45) compared FEC1/2 vs. CMF1/2 (see table below). At 4.5 years there was no difference in disease free survival (DFS), p=0.61; or overall survival (OS), p=0.31. However, subset analysis suggested that FEC2 was better than CMF2 (DFS:p=0.03;OS:p=0.02). Concurrently a study in node negative (N-) patients was conducted comparing FEC2 with CMF2. This paper updates the previous N+ study, reports N- study outcome, and a combined meta analysis (MA). Methods: Prospective MA of two international randomised trials of CMF vs. FEC chemotherapy in early breast cancer: 1) N+ premenopausal trial, 2 regime options (CMF1/FEC1, CMF2/FEC2). and 2) N- trial (CMF2/FEC2). Main endpoints are OS and DFS. Sample sizes are small by today's standards, hence the prospective MA. Results: N+ recruited 759 (180 CMF1, 180 FEC1, 199 CMF2, 200 FEC2) patients between 1984–1992, median follow-up 100 months. N- recruited 950 (477 CMF2, 473 FEC2) patients between 1990–2000, median follow-up 70 months. Median age was 44 (N+) and 48 (N-) years. Grade 3/4 toxicity (sore mouth, vomiting/nausea, diarrhoea, anorexia, alopecia) occurred twice as often with FEC (54%) than CMF (24%), p<0.001. Grade 3/4 toxicity in N+ (56%) was twice that of N- (25%) patients, p<0.001. MA hazard ratios showed that for OS, CMF was better 1.08 (95% CI 0.87 –1.35, p=0.49) but for DFS, FEC was better 0.97 (95% CI 0.82–1.16, p=0.76). Tests showed OS trial results were heterogeneous (p=0.04) with FEC1 better than CMF1 (p=0.04), and CMF2 better than FEC2 (p=0.06) for N+ but no difference for N- (p=0.87). Conclusions: MA showed no difference between the treatments in terms of OS or DFS. Individual trial results for OS were not homogeneous. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aventis Aventis; Eli Lilly