Long-term benefit of high-dose epirubicin in adjuvant chemotherapy for node-positive breast cancer: 15-year efficacy results of the Belgian multicentre study.
OBJECTIVE
The 4-year results of this trial demonstrated that a higher dose of epirubicin with cyclophosphamide (HEC) is superior to a lower dose of epirubicin, 60 mg/m(2) (EC), for event-free survival (EFS; 27% reduction), but is not superior to classical oral cyclophosphamide, methotrexate, and fluorouracil (CMF) in the adjuvant treatment of node-positive breast cancer. Herein we report the 15-year data on efficacy and long-term toxicity of this three-arm Belgian multicenter trial.


METHODS
Between March 1988 and December 1996, 777 eligible patients were randomly assigned to six cycles of CMF, eight cycles of EC, or eight cycles HEC.


RESULTS
The 15-year EFS was 45% for patients who received CMF, 39% for patients who received EC, and 50% for patients who received HEC. The hazard ratios (HR) were 0.77 for HEC versus EC (95% CI, 0.60 to 0.98; P = .03), 0.90 for HEC versus CMF (P = .39), and 0.86 for EC versus CMF (P = .21). No difference in overall survival (OS) was seen. Cardiac toxicity was more frequent with HEC than with CMF (11 patients v 1 patient; P = .006), but no more than with EC (P = .21).


CONCLUSIONS
Treatment with HEC demonstrated superior EFS when compared with lower-dose epirubicin. However, we do not recommend the use of HEC regimen in daily clinical practice, mainly because of the higher risk of cardiotoxicity related to the cumulative doses of epirubicin and the lack of superiority of anthracyclines over CMF in our study.
de Azambuja
Evandro
E
Institut Jules Bordet and Université Libre de Bruxelles, Brussels.
Paesmans
Marianne
M
Beauduin
Marc
M
Vindevoghel
Anita
A
Cornez
Nathalie
N
Finet
Claude
C
Ries
Fernand
F
Closon-Dejardin
Marie Thérèse
MT
Kerger
Joseph
J
Gobert
Philippe
P
Focan
Christian
C
Tagnon
Alain
A
Dolci
Stella
S
Nogaret
Jean M
JM
di Leo
Angelo
A
Piccart-Gebhart
Martine J
MJ
D000328:Adult; D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage*; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001530:Belgium; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D015251:Epirubicin / Q000008:administration & dosage*; D005260:Female; D005472:Fluorouracil; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology; D008727:Methotrexate; D008875:Middle Aged
D000903:Antibiotics, Antineoplastic; D018906:Antineoplastic Agents, Alkylating; D015251:Epirubicin; D003520:Cyclophosphamide; D005472:Fluorouracil; D008727:Methotrexate