A PHASE III RANDOMIZED TRIAL COMPARING ADJUVANT CONCOMITANT CHEMORADIOTHERAPY VERSUS STANDARD ADJUVANT CHEMOTHERAPY FOLLOWED BY RADIOTHERAPY IN OPERABLE NODE-POSITIVE BREAST CANCER: FINAL RESULTS

Purpose: To compare concomitant and sequential adjuvant chemoradiotherapy regimens in node-positive, operable breast cancer patients. Methods and Materials: This was a randomized, French, multicenter, phase III trial enrolling 638 eligible women with prior breast surgery and positive axillary dissection. Patients in Arm A received 500 mg/m 2 5-fluorouracil, 12 mg/m 2 mitoxantrone, and 500 mg/m 2 cyclophosphamide, with concomitant radiotherapy (50 Gy ± 10–20-Gy boost). Patients in Arm B received 500 mg/m 2 5-fluorouracil, 60 mg/m 2 epirubicin, and 500 mg/m 2 cyclophosphamide, with subsequent radiotherapy. Chemotherapy was administered on Day 1 every 21 days for 4 cycles. Results: Median treatment durations were 64 and 126 days (Arms A and B, respectively), with no significant difference in overall or disease-free survival. Five-year locoregional relapse-free survival favored patients with conservative surgery (two thirds of the population), with less local and/or regional recurrence in Arm A than in Arm B (3% vs. 9%; p = 0.01). Multivariate analysis in this subgroup showed a 2.8-fold increased risk of locoregional recurrence with sequential chemoradiotherapy, independent of other prognostic factors ( p = 0.027). Febrile neutropenia and Grade 3–4 leukopenia were significantly more frequent in Arm A. Subclinical left ventricular ejection fraction events at 1 year were more frequent with concomitant radiotherapy ( p = 0.02). Conclusions: Concomitant radiotherapy with adjuvant fluorouracil, mitoxantrone, and cyclophosphamide has significantly better locoregional control in node-positive breast cancer after conservative surgery and 50% shorter treatment, albeit with slightly more acute toxicity. With mitoxantrone no longer available for adjuvant breast cancer treatment, alternative concomitant chemoradiotherapy studies are needed.