Randomized Trial Comparing Cyclophosphamide, Epirubicin, and Fluorouracil With Cyclophosphamide, Methotrexate, and Fluorouracil in Premenopausal Women With Node-Positive Breast Cancer: Update of National Cancer Institute of Canada Clinical Trials Group Trial MA5

• Published in: Journal of clinical oncology Vol. 23; no. 22; pp. 5166 - 5170
• Main Authors: LEVINE, Mark N, PRITCHARD, Kathleen I, BRAMWELL, Vivien H. C, SHEPHERD, Lois E, DONGSHENG TU, PAUL, Nancy
• Format: Journal Article
• Language: English
• Published: Baltimore, MD American Society of Clinical Oncology 01.08.2005; Lippincott Williams & Wilkins
• Subjects: Administration, Oral; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Breast Neoplasms - drug therapy; Breast Neoplasms - pathology; Cyclophosphamide - administration & dosage; Epirubicin - administration & dosage; Female; Fluorouracil - administration & dosage; Gynecology. Andrology. Obstetrics; Humans; Infusions, Intravenous; Mammary gland diseases; Medical sciences; Methotrexate - administration & dosage; Middle Aged; Premenopause; Tumors; Canada; North America; America; Antineoplastic agent; Antifolate; Cancerology; Adult; Clinical trial; Female; Epirubicin; Methotrexate; Fluorouracil; Human; Premenopause; Enzyme; Fluoropyrimidine derivatives; Transferases; Enzyme inhibitor; Breast cancer; Malignant tumor; Thymidylate synthase; Mammary gland diseases; Alkylating agent; Oxazaphosphinane derivatives; Cyclophosphamide; Antimetabolic; Methyltransferases; Nitrogen mustard; Pyrimidine derivatives; Anthracyclins
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/JCO.2005.09.423

Certain anthracycline-containing adjuvant chemotherapy regimens are associated with improved relapse-free survival (RFS) and overall survival (OS) compared with the classic regimen of cyclophosphamide, methotrexate, and fluorouracil in women with early-stage breast cancer. Between 1989 and 1993, 710 pre- and perimenopausal women with axillary node-positive breast cancer were randomly assigned to either cyclophosphamide 75 mg/m(2) orally days 1 through 14, epirubicin 60 mg/m(2) intravenously days 1 and 8, and fluorouracil 500 mg/m(2) intravenously days 1 and 8 (CEF) or CMF (cyclophosphamide 100 mg/m(2) orally days 1 through 14, methotrexate 40 mg/m(2) intravenously days 1 and 8, and fluorouracil 600 mg/m(2) intravenously days 1 and 8). On the basis of follow-up to May 1997 (median follow-up time, 59 months), there was a statistically significant improvement in RFS and OS for CEF compared with CMF. The trial results are now updated, with a median follow-up of 10 years for live patients. The 10-year RFS is 52% for patients who received CEF compared with 45% for CMF patients (hazard ratio [HR] for CMF v CEF = 1.31; stratified log-rank, P = .007). The 10-year OS for patients who received CEF and CMF are 62% and 58%, respectively (HR for CMF v CEF = 1.18; stratified log-rank, P = .085). The rates of acute leukemia have not changed since the original report, whereas the rates of congestive heart failure are slightly higher but acceptable (four patients [1.1%] in the CEF group v one patient [0.3%] in the CMF group). The previously demonstrated benefit of CEF compared with CMF adjuvant chemotherapy is maintained with longer follow-up in the MA5 trial.