Epirubicin and cyclophosphamide, methotrexate, and fluorouracil as adjuvant therapy for early breast cancer.
BACKGROUND
The National Epirubicin Adjuvant Trial (NEAT) and the BR9601 trial examined the efficacy of anthracyclines in the adjuvant treatment of early breast cancer.


METHODS
In NEAT, we compared four cycles of epirubicin followed by four cycles of cyclophosphamide, methotrexate, and fluorouracil (CMF) with six cycles of CMF alone. In the BR9601 trial, we compared four cycles of epirubicin followed by four cycles of CMF, with eight cycles of CMF alone every 3 weeks. The primary end points were relapse-free and overall survival. The secondary end points were adverse effects, dose intensity, and quality of life.


RESULTS
The two trials included 2391 women with early breast cancer; the median follow-up was 48 months. Relapse-free and overall survival rates were significantly higher in the epirubicin-CMF groups than in the CMF-alone groups (2-year relapse-free survival, 91% vs. 85%; 5-year relapse-free survival, 76% vs. 69%; 2-year overall survival, 95% vs. 92%; 5-year overall survival, 82% vs. 75%; P<0.001 by the log-rank test for all comparisons). Hazard ratios for relapse (or death without relapse) (0.69; 95% confidence interval [CI], 0.58 to 0.82; P<0.001) and death from any cause (0.67; 95% CI, 0.55 to 0.82; P<0.001) favored epirubicin plus CMF over CMF alone. Independent prognostic factors were nodal status, tumor grade, tumor size, and estrogen-receptor status (P<0.001 for all four factors) and the presence or absence of vascular or lymphatic invasion (P=0.01). These factors did not significantly interact with the effect of epirubicin plus CMF. The overall incidence of adverse effects was significantly higher with epirubicin plus CMF than with CMF alone but did not significantly affect the delivered-dose intensity or the quality of life.


CONCLUSIONS
Epirubicin plus CMF is superior to CMF alone as adjuvant treatment for early breast cancer. (ClinicalTrials.gov number, NCT00003577 [ClinicalTrials.gov].).
Poole
Christopher J
CJ
Cancer Research UK Clinical Trials Unit, Institute for Cancer Studies, University of Birmingham, Birmingham, United Kingdom. poolecj@aol.com
Earl
Helena M
HM
Hiller
Louise
L
Dunn
Janet A
JA
Bathers
Sarah
S
Grieve
Robert J
RJ
Spooner
David A
DA
Agrawal
Rajiv K
RK
Fernando
Indrajit N
IN
Brunt
A Murray
AM
O'Reilly
Susan M
SM
Crawford
S Michael
SM
Rea
Daniel W
DW
Simmonds
Peter
P
Mansi
Janine L
JL
Stanley
Andrew
A
Harvey
Peter
P
McAdam
Karen
K
Foster
Liz
L
Leonard
Robert C F
RC
Twelves
Christopher J
CJ
D000704:Analysis of Variance; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000601:surgery*; D017024:Chemotherapy, Adjuvant; D003520:Cyclophosphamide / Q000008:administration & dosage; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D005500:Follow-Up Studies; D006801:Humans; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D011788:Quality of Life; D012008:Recurrence; D016019:Survival Analysis
D015251:Epirubicin; D003520:Cyclophosphamide; D005472:Fluorouracil; D008727:Methotrexate