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Randomized Trial Comparing Six Versus Three Cycles of Epirubicin-Based Adjuvant Chemotherapy in Premenopausal, Node-Positive Breast Cancer Patients: 10-Year Follow-Up Results of the French Adjuvant Study Group 01 Trial

Pierre Fumoleau, Pierre Kerbrat, Pascale Romestaing, Pierre Fargeot, Alain Brémond, Moïse Namer, Simon Schraub, Marie-Jo Goudier, Jeanne Mihura, Alain Monnier, Pierre Clavère, Daniel Serin, Philippe Seffert, Christiane Pourny, Thomas Facchini, Jean-Philippe Jacquin, Jean-François Sztermer, Jean Datchary, René Ramos, Elisabeth Luporsi

From the Centre René Gauducheau, Nantes; Centre Eugéne Marquis, Rennes; Centre Hospitalier de Lyon Sud; Centre Léon Bérard, Lyon; Centre Georges-François Leclerc, Dijon; Centre Antoine Lacassagne, Nice; Centre Hospitalier Jean Minjoz, Besançon; Centre Hospitalier de Bretagne Sud, Lorient; Institut Claudius Régaud, Toulouse; Centre Hopsitalier André Boulloche, Montbéliard; Centre Hospitalier Universitaire Dupuytren, Limoges; Clinique Sainte-Catherine, Avignon; Institut Jean Godinot, Reims; Hôpital Nord; Clinique Radiologique et Orthopédique, Saint-Etienne; Hôpital Notre-Dame de Bon Secours, Metz; Centre Hospitalier Jean Monnet, Epinal; Institut Gustave Roussy, Villejuif; Centre Hospitalier Général, Troyes; Centre Hospitalier, Annecy; Clinique le Méridien, Cannes; Centre Hospitalier Général, Montélimar; Centre Jean Perrin, Clermont-Ferrand; Centre Hositalier Général, Belfort; and Centre Hospitalier Général, Tarbes, France.

Address reprint requests to Pierre Fumoleau, MD, Département d’Oncologie Médicale, Centre René Gauducheau, Boulevard Jacques Monod, 44805 Nantes Saint-Herblain, France; email: fumoleau{at}gauducheau-nantes.fnclcc.fr.

Purpose: To evaluate the duration and dose intensity of epirubicin-based regimens in premenopausal patients with lymph node-positive breast cancer.

Patients and Methods: Between 1986 and 1990, 621 patients with operable breast cancer were randomly assigned to receive fluorouracil (Roche SA, Basel, Switzerland) 500 mg/m², epirubicin (Pharmacia SA, Milan, Italy) 50 mg/m², and cyclophosphamide (Asta Medica AG, Frankfurt, Germany) 500 mg/m² every 21 days (FEC 50) for six cycles (6 FEC 50); FEC 50 for three cycles (3 FEC 50); or the same regimen with epirubicin 75 mg/m² (FEC 75) for three cycles (3 FEC 75). All patients in the three arms received chest wall irradiation at the end of the third cycle.

Results: After a 131-month median follow-up, the 10-year disease-free survival (DFS) was 53.4%, 42.5%, and 43.6% (P = .05) in the three arms, respectively. Pairwise comparisons demonstrate that 6 FEC 50 was superior both to 3 FEC 50 (P = .02) and to 3 FEC 75 (P = .05). The 10-year overall survival (OS) for the 6 FEC 50 arm was 64.3%, for the 3 FEC 50 arm it was 56.6%, and for the 3 FEC 75 arm, it was 59.7% (P = .25), respectively. Pairwise comparisons demonstrate that 6 FEC 50 was more effective than 3 FEC 50 (P = .10). Cox regression analysis demonstrates that OS was significantly better in the 6 FEC 50 than in the 3 FEC 50 arm (P = .046). No severe infections (grade 3 to 4), acute cardiac toxicity, or deaths from toxicity have been observed. Only five patients developed delayed cardiac dysfunctions, and three patients developed acute myeloblastic leukemia.

Conclusion: After a long-term follow-up in an adjuvant setting, the benefit of six cycles of FEC 50 compared with three cycles, whatever the dose, is highly significant in terms of DFS. As regards OS, the group receiving six cycles of FEC 50 has significantly better results than the group receiving three cycles of FEC 50.

Supported by grants from Pharmacia and Upjohn, Saint-Quentin en Yvelines, France.

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