Optimizing adjuvant breast cancer chemotherapy: rationale for the MA.21 study.

Recently initiated is a phase III randomized trial (MA.21 trial) of adjuvant chemotherapy for node-positive and high-risk node-negative, premenopausal and postmenopausal (< or = 60 years) women with breast cancer who have no distant metastases. Conducted by the National Cancer Institute of Canada-Clinical Trials Group, the trial will compare two standard therapies, CEF (cyclophosphamide [Cytoxan, Neosar], epirubicin [Ellence], fluorouracil) and AC-->T (doxorubicin [Adriamycin], cyclophosphamide, followed by paclitaxel [Taxol]), and includes a third arm consisting of a dose-dense, dose-intense EC-->T regimen (epirubicin, cyclophosphamide, followed by paclitaxel). These regimens were chosen for study based on results of previous clinical assessments of adjuvant therapies, which, taken together, suggest that CEF, FEC 100 (where 100 represents the dose in mg/m2 of epirubicin in FEC [fluorouracil, epirubicin, cyclophosphamide]), CAF (cyclophosphamide, doxorubicin, fluorouracil), and AC-->T may all be superior to standard AC or CMF (cyclophosphamide, methotrexate, fluorouracil) regimens. This article reviews trial results that support the testing of the regimens chosen for the MA.21 trial. The intent of the MA.21 study is to advance our ability to provide optimal adjuvant therapy for patients with breast cancer.