title: Improved outcome from substituting methotrexate with epirubicin: results from a randomised comparison of CMF versus CEF in patients with primary breast cancer.
abstract: We compared the efficacy of CEF (cyclophosphamide, epirubicin, and fluorouracil) against CMF (cyclophosphamide, methotrexate, and fluorouracil) in moderate or high risk breast cancer patients. We randomly assigned 1224 patients with completely resected unilateral breast cancer to receive nine cycles of three-weekly intravenous CMF or CEF. Patients were encouraged to take part in a parallel trial comparing oral pamidronate 150 mg twice daily for 4 years versus control (data not shown). Substitution of methotrexate with epirubicin significantly reduced the unadjusted hazard for disease-free survival (DFS) by 16% (hazard ratio 0.84; 95% CI; 0.71-0.99) and for overall survival by 21% (hazard ratio 0.79; 95% CI; 0.66-0.94). The risk of secondary leukaemia and congestive heart failure was similar in the two groups. Overall CEF was superior over CMF in terms of DFS and OS in patients with operable breast cancer without subsequent increase in late toxicities.
authors.affiliation: Department of Oncology, Bldg. 5012 Rigshospitalet, Copenhagen University Hospital, 9. Blegdamsvej, DK-2100 Copenhagen, Denmark. ejlertsen@rh.dk
authors.forename: Bent
authors.initials: B
authors.lastname: Ejlertsen
authors.forename: Henning T
authors.initials: HT
authors.lastname: Mouridsen
authors.forename: Maj-Britt
authors.initials: MB
authors.lastname: Jensen
authors.forename: Jørn
authors.initials: J
authors.lastname: Andersen
authors.forename: Søren
authors.initials: S
authors.lastname: Cold
authors.forename: Per
authors.initials: P
authors.lastname: Edlund
authors.forename: Marianne
authors.initials: M
authors.lastname: Ewertz
authors.forename: Brita B
authors.initials: BB
authors.lastname: Jensen
authors.forename: Claus
authors.initials: C
authors.lastname: Kamby
authors.forename: Bo
authors.initials: B
authors.lastname: Nordenskjold
authors.forename: Jonas
authors.initials: J
authors.lastname: Bergh
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy*; D003520:Cyclophosphamide / Q000008:administration & dosage; D003561:Cytarabine / Q000008:administration & dosage; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D016896:Treatment Outcome
chemical_list: D003561:Cytarabine; D015251:Epirubicin; D003520:Cyclophosphamide; D005472:Fluorouracil; D008727:Methotrexate