Randomized Phase Iii Trial Of Adjuvant Epicirubicin (E) Followed By Cyclophosphamide, Methotrexate, And Fluorouracil (Cmf) Or Cmf Followed By E In Patients With N- Or <= 3 N+ Rapidly Proliferating Breast Cancer (Rpbc)

560 Background: Antimetabolites are active in proliferating cells, and the adjuvant schedule CMF is highly effective in RPBC, whereas the sequential administration of doxorubicin (D) and CMF is superior to CMF–u003eD, especially in indolent tumors. In a phase III study, we evaluated whether adjuvant E followed by CMF is superior to the inverse sequence in RPBC. Methods: Patients with N-, T u003e 1 cm or ≤ 3 N+ and any T RPBC (defined by thymidine labeling index or grade or S-phase or Ki67/MIB1) were randomized to receive E (100 mg/m2 i.v. d 1, q 21 days for 4 cycles) followed by CMF (600, 40, 600 mg/m2 i.v. d 1 and 8, q 28 days for 4 cycles) (arm A) or CMF followed by E (arm B) or CMF (600, 40, 600 mg/m2 i.v. d 1 and 8, q 28 days for 6 cycles) (arm C). Arm C was closed after the EBCTCG 2000 meta-analysis (data not shown). The main endpoint was overall survival (OS), and the study had 80% power to detect a 7% absolute increase in 5-year OS with 400 patients per arm. Results: From November 1997 to December 2004, 10...