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


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.


CONCLUSIONS
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.
Fumoleau
Pierre
P
Département d'Oncologie Médicale, Centre René Gauducheau, Nantes, France. fumoleau@gauducheau-nantes.fnclcc.fr
Kerbrat
Pierre
P
Romestaing
Pascale
P
Fargeot
Pierre
P
Brémond
Alain
A
Namer
Moïse
M
Schraub
Simon
S
Goudier
Marie-Jo
MJ
Mihura
Jeanne
J
Monnier
Alain
A
Clavère
Pierre
P
Serin
Daniel
D
Seffert
Philippe
P
Pourny
Christiane
C
Facchini
Thomas
T
Jacquin
Jean-Philippe
JP
Sztermer
Jean-François
JF
Datchary
Jean
J
Ramos
René
R
Luporsi
Elisabeth
E
D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D015251:Epirubicin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D005500:Follow-Up Studies; D006331:Heart Diseases / Q000139:chemically induced; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology; D008207:Lymphatic Metastasis; D008875:Middle Aged; D017697:Premenopause; D012307:Risk Factors; D015996:Survival Rate
D015251:Epirubicin; D003520:Cyclophosphamide; D005472:Fluorouracil