Originally published as JCO Early Release 10.1200/JCO.2008.17.2155 on December 22 2008

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Long-Term Benefit of High-Dose Epirubicin in Adjuvant Chemotherapy for Node-Positive Breast Cancer: 15-Year Efficacy Results of the Belgian Multicentre Study

From the Institut Jules Bordet and Université Libre de Bruxelles, Brussels; Hopital de Jolimont-Lobbes; Centre Hospitalier Universitaire de Tivoli, La Louvière; Clinique Sainte Elisabeth, Namur; Hôpital de Braine L'Alleud, Waterloo; Centre Hospitalier Universitaire de Liège; Centre Hospitalier Chrétien, Liège; Service d'Oncologie, Cliniques Universitaires Université Catholique de Louvain, Godinne; Clinique Saint-Joseph, Arlon; Réseau Hospitalier de Médecine Sociale, Tournai, Belgium; Programa de Pós-graduação em Medicina: Ciências Médicas, Faculdade de Medicina, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil; Centre Hospitalier de Luxembourg, Luxembourg; and Hospital of Prato, Prato, Italy.

Corresponding author: Martine Piccart-Gebhart, MD, PhD, Jules Bordet Institute, Blvd de Waterloo 125, 1000 Brussels, Belgium; e-mail: martine.piccart{at}bordet.be.

Purpose 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/m² (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.

Patients and 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).

Conclusion 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.

Supported by Pharmacia (research grant to Institut Jules Bordet) and Pfizer (M.J.P.-G.).

Presented in part at the 42nd Annual Meeting of the American Society of Clinical Oncology, June 2-6, 2006, Atlanta, GA.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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