Benefit of a high-dose epirubicin regimen in adjuvant chemotherapy for node-positive breast cancer patients with poor prognostic factors: 5-year follow-up results of French adjuvant study group 05 randomized trial

Purpose: To determine the influence of the epirubicin dose in operable node -positive breast cancer patients with factors of poor prognosis. Patients and Methods: Between April 1990 and July 1993, 565 operable breast cancer patients with either more than three positive nodes or between one and three positive nodes with Scarff Bloom Richardson grade greater than or equal to 2 and hormone receptor negativity were randomized after surgery t o receive either fluorouracil 500 mg/m(2), epirubicin 50 mg/m(2), and cyclo phosphamide 500 mg/m(2) every 21 days for six cycles (FEC 50) or the same r egimen except with epirubicin dose of 100 mg/m(2) (FEC 100). Postmenopausal patients received tamoxifen 30 mg/d for 3 years at the beginning of chemot herapy. Radiotherapy was delivered at the end of chemotherapy in both group s. Results: The median follow-vp was 67 months. The 5-year disease-free surviv al (DFS) was 54.8% with FEC 50 and 66.3% with FEC 100 (P = .03). The 5-year overall survival (OS) was 65.3% and 77.4%, respectively (P = .007). The me an relative dose intensity was similar in the two groups (90.3% and 86.1%, respectively). Neutropenia and anemia were significantly more frequent in F EC 100 (P < 10(-3)), as were nausea-vomiting (P = .008) and stomatitis and alopecia (P < 10(-3)). Nine cases of grade 3 infection occurred only with F EC 100, and no toxic deaths occurred. Three cases of acute cardiac toxicity were observed (FEC50 = 1, FEC100 = 2) and 10 patients (FEC50 = 6, FEC100 = 4) presented delayed cardiac dysfunctions. Two cases of secondary leukemia were observed (acute lymphatic leukemia with FEC 50 and acute myelogenous leukemia with FEC 100). Conclusion: After 5 years of follow up, the increased epirubicin dose led t o a significant benefit in terms of DFS and OS, with a high survival rate a mong patients with poor-prognosis breast cancer. (C) 2001 by American Socie ty of Clinical Oncology.