Randomized phase III trial of adjuvant epirubicin followed by cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) versus CMF followed by epirubicin in patients with node-negative or 1–3 node-positive rapidly proliferating breast cancer

International audience; Adjuvant cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) have proven highly effective in rapidly proliferating breast cancer (RPBC). It has also been seen that sequential administration of doxorubicin and CMF is superior to their alternation, especially in indolent tumors. In a phase III study, we evaluated whether adjuvant epirubicin (E) followed by CMF is superior to the inverse sequence in RPBC. Patients with node-negative or 1-3 node-positive RPBC (Thymidine Labeling Index > 3% or histological grade 3 or S-phase > 10% or Ki67 > 20%) were randomized to receive E (100 mg/m i.v. d1, q21 days for 4 cycles) followed by CMF (600, 40, 600 mg/m i.v. d1 and 8, q2…