Anthracycline-based sequential adjuvant chemotherapy in operable breast cancer: Five-year results of a randomized study by the Michelangelo Foundation

Abstract

535 Background: Anthracycline-based sequential chemotherapy significantly improves efficacy outcomes compared to CMF alone. Methods: 806 eligible patients with operable breast cancer were enrolled into a randomized study (ratio 1:1:1:1) of sequential chemotherapy. In a 2×2-type design patients were allocated to first receive 4 cycles of AT (doxorubicin, A 60 mg/m2 iv + paclitaxel, T 200 mg/m2 as 3 h inf q 3wks) or EV (epirubicin, E 75 mg/m2 iv + vinorelbine, V 25 mg/m2 iv D1,8 q3wks) followed either by 4 monthly cycles of iv CMF or 6 cycles of q3w T alone (100 mg/m2 as 1h inf D1,8). Tamoxifen was recommended for 5 yr after chemotherapy in patients with HR+ tumors. Patients with tumors > 2 cm in diameter were allowed to start primary chemotherapy with 4 cycles of either AT or EV followed by surgery and postoperative systemic treatment as detailed above. Aim of the study was to test the role of T vs V when combined with an anthracycline during the first 4 cycles of the regimen as well as the role of CMF vs T during the last 4 cycles. Results: At a median follow-up of approximately 48 months, the 5 year freedom from progression (FFP) and overall survival (OS) for the main endpoints were as in the Table : The four treatment sequences were fairly well tolerated, with only 1 treatment-related death after EV. Type and severity of hematological toxicities were similar in all treatment arms. The incidence of reversible G2–3 neurotoxicity was 21.9% after AT, 5.3% after EV and 29.1% after sequential T. Chemical phlebitis was more frequent after EV (6.5%) then after AT (0.3). Conclusions: The results indicate that vinorelbine-epirubicin and classical CMF when appropriately used in a sequential modality for high-risk breast cancer are as valid and less neurotoxic an option of adjuvant therapy than the more widely used taxane-containing adjuvant regimens. Supported in part by Bristol-Myers Squibb, Pierre Fabre and Pharmacia. [Table: see text] [Table: see text]