Epirubicin Increases Long-Term Survival in Adjuvant Chemotherapy of Patients With Poor-Prognosis, Node-Positive, Early Breast Cancer: 10-Year Follow-Up Results of the French Adjuvant Study Group 05 Randomized Trial

• Published in: Journal of clinical oncology Vol. 23; no. 12; pp. 2686 - 2693
• Main Authors: BONNETERRE, Jacques, ROCHE, Henri, KERBRAT, Pierre, BREMOND, Alain, FUMOLEAU, Pierre, NAMER, Moïse, GOUDIER, Marie-Josèphe, SCHRAUB, Simon, FARGEOT, Pierre, CHAPELLE-MARCILLAC, Isabelle
• Format: Journal Article
• Language: English
• Published: Baltimore, MD American Society of Clinical Oncology 20-04-2005; Lippincott Williams & Wilkins
• Subjects: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Breast Neoplasms - drug therapy; Breast Neoplasms - pathology; Chemotherapy, Adjuvant; Cyclophosphamide - administration & dosage; Disease-Free Survival; Dose-Response Relationship, Drug; Epirubicin - administration & dosage; Female; Fluorouracil - administration & dosage; Follow-Up Studies; Heart - drug effects; Humans; Infusions, Intravenous; Medical sciences; Middle Aged; Neoplasms, Second Primary; Prognosis; Tumors; Antineoplastic agent; Human; Prognosis; Adjuvant treatment; Patient; Breast cancer; Malignant tumor; Long term; Survival; Mammary gland diseases; Cancerology; Clinical trial; Anthracyclins; Adjuvant; Epirubicin
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/JCO.2005.05.059

The French Adjuvant Study Group 05 (FASG-05) showed that fluorouracil 500 mg/m2, cyclophosphamide 500 mg/m2, and epirubicin 100 mg/m2 (FEC 100) was superior to the same regimen with epirubicin 50 mg/m2 (FEC 50) in terms of disease-free survival (DFS) and overall survival (OS) in adjuvant treatment of early breast cancer. We report 10-year data on efficacy, and long-term side effects for FASG-05.
We randomly assigned 565 patients to treatment with FEC 50 or FEC 100 after surgery. Postmenopausal patients also received tamoxifen for 3 years, and almost all patients (96%) also received radiotherapy.
Median follow-up was 110 months. The 10-year DFS was 45.3% (95% CI, 41.9% to 48.7%) with FEC 50 and 50.7% (95% CI, 47.3% to 54.1%) with FEC 100 (Wilcoxon P = .036; log-rank P = .08). The 10-year OS was 50.0% (95% CI, 46.7% to 53.3%) with FEC 50 and 54.8% (95% CI, 51.3% to 58.3%) with FEC 100 (Wilcoxon P = .038; log-rank P = .05). Delayed cardiac toxicity (before relapse) occurred in four patients (1.5%) in the FEC 50 arm and three patients (1.1%) in the FEC 100 arm. Cardiac toxicity after relapse occurred in six (4.3%) and five (4.1%) patients treated with FEC 50 and FEC 100, respectively.
Treatment with adjuvant FEC 100 demonstrated superior DFS and OS versus FEC 50 at 10 years of follow-up. This survival advantage was not offset by long-term complications such as cardiac toxicity and second malignancy. Given the risk-benefit ratio, FEC 100 is a more optimal regimen for long-term survival in patients with poor prognosis.