Epirubicin plus tamoxifen versus tamoxifen alone in node-positive postmenopausal patients with breast cancer: A randomized trial of the InternationalCollaborative Cancer Group

Purpose: To assess whether the addition of epirubicin (EPI) therapy to prol onged treatment with tamoxifen (TAM) improves relapse-free and overall surv ival in postmenopausal women with node-positive primary breast cancer. Patients and Methods: Six hundred four patients entered onto a randomized c linical trial were allocated to receive TAM 20 mg/d for 4 years or TAM 20 m g/d for 4 years plus EPI 50 mg/m(2) intravenously on days 1 and 8 every 4 w eeks for six cycles. Analysis was performed according to allocated treatmen t, with all randomized patients included (intention to treat), irrespective of eligibility status. Results: After a median follow-up period of 5.7 years, an improvement in re lapse-free survival (RFS) was observed for the TAM and EPI-treated patients , compared with those who received TAM alone. The unadjusted hazard ratio w as 0.72 (95% confidence interval, 0.54 to 0.96), with a corresponding reduc tion in the odds of recurrence of 27.9% (SD, 12.3), which was statistically significant (P = .023), Adjustment for prognostic and/or predictive factor s did not materially affect the hazard ratio. No difference was observed in terms of overall survival (reduction in odds of death, 11.9% [SD, 16.3]; P = .46). Combined chemohormonal treatment was associated with a higher inci dence of acute side effects but without a clear increase in long-term cardi otoxicity. Twelve nonbreast second malignancies, including five hematologic malignancies (two of which were cases of acute myelogenous leukemia), were observed. Conclusion: The data show that combined chemohormonal treatment reduces the risk of relapse in postmenopausal patients with node-positive breast cance r. No evidence was found, however, for an improvement in overall survival. The size of benefit observed for both outcomes was consistent with that rep orted in the Early breast Cancer Trialists' Collaborative Group overview. T he trial presented here, however, provides the first report of an improveme nt in RFS associated with the provision of a single cytotoxic drug in addit ion to prolonged TAM. (C) 1999 by American Society of Clinical Oncology.