Disease-free survival advantage of weekly epirubicin plus tamoxifen versus tamoxifen alone as adjuvant treatment of operable, node-positive, elderly breast cancer patients: 6-year follow-up results of the French adjuvant study group 08 trial

J Clin Oncol. 2004 Dec 1;22(23):4622-30. doi: 10.1200/JCO.2004.02.145. Epub 2004 Oct 25.

Abstract

Purpose: To assess whether an epirubicin (EPI) -based chemotherapy plus hormonal regimen improves disease-free (DFS) in women older than 65 years, with node-positive, operable breast cancer (BC), relative to tamoxifen (TAM) alone.

Patients and methods: A total of 338 patients were randomly assigned after surgery to receive TAM 30 mg/d for 3 years (TAM, n = 164), or EPI 30 mg on days 1, 8, and 15 every 28 days for six cycles plus TAM 30 mg/d for 3 years (EPI-TAM, n = 174). In both arms, patients received radiotherapy, delivered after chemotherapy (CT) in the EPI-TAM group.

Results: The 6-year DFS rates were 69.3% with TAM and 72.6% with EPI-TAM (P = .14). The multivariate analysis shows a relative risk of relapse of 1.93 (95% CI, 1.70 to 2.17) with TAM compared with EPI-TAM (P = .005). The 6-year OS, related to disease progression, was 79.1% and 79.8%, respectively (P = .41). Compliance with CT was good: 96.9% of patients received six cycles. The acute toxicity per patient was mild: grade 2 neutropenia in 5.9%, grade 2 anemia in 2.0%, grade 3 nausea or vomiting in 4.6%, and grade 3 alopecia in 7.2%. Five cases (in five patients) of decreased left ventricular ejection fraction occurred after CT: three after adjuvant CT, and two after anthracycline-based CT for relapse. One patient died as a result of dysrhythmia related to carcinomatous lymphangitis. No secondary leukemia occurred.

Conclusion: This study conducted in node-positive elderly patients demonstrates a significant contribution of a weekly EPI regimen in terms of DFS. Moreover, this regimen is safe for hematologic, nonhematologic, and cardiac toxicities.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Biopsy, Needle
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / mortality*
  • Breast Neoplasms / pathology
  • Breast Neoplasms / surgery
  • Disease-Free Survival
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Epirubicin / administration & dosage*
  • Female
  • Humans
  • Immunohistochemistry
  • Lymph Nodes / pathology*
  • Lymphatic Metastasis
  • Mastectomy / methods
  • Maximum Tolerated Dose
  • Menopause
  • Neoplasm Invasiveness / pathology
  • Neoplasm Staging
  • Prognosis
  • Risk Assessment
  • Survival Rate
  • Tamoxifen / administration & dosage*
  • Treatment Outcome

Substances

  • Tamoxifen
  • Epirubicin