title: 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.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  The previously demonstrated benefit of CEF compared with CMF adjuvant chemotherapy is maintained with longer follow-up in the MA5 trial.
authors.affiliation: Department of Clinical Epidemiology, McMaster University, Hamilton, Ontario, Canada. mlevine@mcmaster.ca
authors.forename: Mark N
authors.initials: MN
authors.lastname: Levine
authors.forename: Kathleen I
authors.initials: KI
authors.lastname: Pritchard
authors.forename: Vivien H C
authors.initials: VH
authors.lastname: Bramwell
authors.forename: Lois E
authors.initials: LE
authors.lastname: Shepherd
authors.forename: Dongsheng
authors.initials: D
authors.lastname: Tu
authors.forename: Nancy
authors.initials: N
authors.lastname: Paul
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D003520:Cyclophosphamide / Q000008:administration & dosage; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D007262:Infusions, Intravenous; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D017697:Premenopause
chemical_list: D015251:Epirubicin; D003520:Cyclophosphamide; D005472:Fluorouracil; D008727:Methotrexate