ABSTRACT
By comparing three schedules of CAF (cyclophosphamide, doxorubicin, and 5-FU), this was the first study to prospectively demonstrate a threshold dose intensity of adjuvant CT for breast cancer below which disease-free and overall survival were compromised. The 3 arms were: (1) 4 C 600 d1, A 60 d1, F 600 d1,8 q28d; (2) 6 C 400 d1, A 40 d1, F 400 d1,8 q28d; (3) 4 C 300 d1, A 30 d1, F 300 d1,8 q28d (doses given in mg/m2). Ninety-five percent of the patients received at least 90% of their assigned doses; 22 patients received no treatment and were not included in the analysis (together with 21 patients with inadequate follow-up data). Both disease-free and overall survival were significantly poorer in group 3 (low dose intensity and low total dose arm) compared with groups 1 and 2; the differences between groups 1 and 2 were not significant. Benefits favoring the intermediate-and high-dose arms were seen in all subgroups (number of nodes, menopausal status, estrogen receptor status, Tm size, type of surgery). Toxicity was manageable and directly correlated with dose intensity. The disease-free and overall survival differences have been maintained through 9 years of follow-up [35], and the doses given in group 3 are now considered inadequate.
