\u201cA randomised factorial trial of sequential doxorubicin and CMF vs CMF and chemotherapy alone vs chemotherapy followed by goserelin plus tamoxifen as adjuvant treatment of node-positive breast cancer\u201d

Abstract

The sequential doxorubicin \u2192 CMF (CMF = cyclophosphamide, methotrexate, fluorouracil) regimen has never been compared to CMF in a randomised trial. The role of adding goserelin and tamoxifen after chemotherapy is unclear. In all, 466 premenopausal node-positive patients were randomised to: (a) CMF 7 6 cycles (CMF); (b) doxorubicin 7 4 cycles followed by CMF 7 6 cycles (A \u2192 CMF); (c) CMF 7 6 cycles followed by goserelin plus tamoxifen 7 2 years (CMF \u2192 GT); and (d) doxorubicin 7 4 cycles followed by CMF 7 6 cycles followed by goserelin plus tamoxifen 7 2 years (A \u2192 CMF \u2192 GT). The study used a 2 7 2 factorial experimental design to assess: (1) the effect of the chemotherapy regimens (CMF vs A 7 CMF or arms a + c vs b + d) and (2) the effect of adding GT after chemotherapy (arms a + b vs c + d). At a median follow-up of 72 months, A \u2192 CMF as compared to CMF significantly improved disease-free survival (DFS) with a multivariate hazard ratio (HR) = 0.740 (95% confidence interval (CI): 0.556-0.986; P = 0.040) and produced a nonsignificant improvement of overall survival (OS) (HR = 0.764; 95% CI: 0.489-1.193). The addition of GT after chemotherapy significantly improved DFS (HR = 0.74; 95% CI: 0.555-0.987; P = 0.040), with a nonsignificant improvement of OS (HR = 0.84; 95% CI: 0.54-1.32). A \u2192 CMF is superior to CMF. Adding GT after chemotherapy is beneficial for premenopausal node-positive patients. \ua9 2005 Cancer Research UK