Sequential adjuvant epirubicin-based and docetaxel chemotherapy for node-positive breast cancer patients: the FNCLCC PACS 01 Trial.
OBJECTIVE
The PACS 01 trial compared six cycles of fluorouracil, epirubicin, and cyclophosphamide (FEC) with a sequential regimen of three cycles of FEC followed by three cycles of docetaxel (FEC-D) as adjuvant treatment for women with node-positive early breast cancer.


METHODS
Between June 1997 and March 2000, 1,999 patients with operable node-positive breast cancer were randomly assigned to either FEC every 21 days for six cycles, or three cycles of FEC followed by three cycles of docetaxel, both given every 21 days. Hormone-receptor-positive patients received tamoxifen for 5 years after chemotherapy. The primary end point was 5-year disease-free survival (DFS).


RESULTS
Median follow-up was 60 months. Five-year DFS rates were 73.2% with FEC and 78.4% with FEC-D (unadjusted P = .011; adjusted P = .012). Multivariate analysis adjusted for prognostic factors showed an 18% reduction in the relative risk of relapse with FEC-D. Five-year overall survival rates were 86.7% with FEC and 90.7% with FEC-D, demonstrating a 27% reduction in the relative risk of death (unadjusted P = .014; adjusted P = .017). The incidence of grade 3 to 4 neutropenia, the need for hematopoietic growth factor, and incidence of nausea/vomiting were higher with FEC. Docetaxel was associated with more febrile neutropenia in the fourth cycle, stomatitis, edema, and nail disorders. Though rare overall, there were fewer cardiac events after FEC-D (P = .03), attributable mainly to the lower anthracycline cumulative dose.


CONCLUSIONS
Sequential adjuvant chemotherapy with FEC followed by docetaxel significantly improves disease-free and overall survival in node-positive breast cancer patients and has a favorable safety profile.
Roché
Henri
H
Department of Medical Oncology, Institut Claudius Régaud, Toulouse, France. roche.henri@claudiusregaud.fr
Fumoleau
Pierre
P
Spielmann
Marc
M
Canon
Jean-Luc
JL
Delozier
Thierry
T
Serin
Daniel
D
Symann
Michel
M
Kerbrat
Pierre
P
Soulié
Patrick
P
Eichler
Françoise
F
Viens
Patrice
P
Monnier
Alain
A
Vindevoghel
Anita
A
Campone
Mario
M
Goudier
Marie-Josèphe
MJ
Bonneterre
Jacques
J
Ferrero
Jean-Marc
JM
Martin
Anne-Laure
AL
Genève
Jean
J
Asselain
Bernard
B
D000328:Adult; D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; 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; D018572:Disease-Free Survival; D000077143:Docetaxel; D004334:Drug Administration Schedule; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D008207:Lymphatic Metastasis; D008875:Middle Aged; D013629:Tamoxifen / Q000627:therapeutic use; D043823:Taxoids / Q000008:administration & dosage; D016896:Treatment Outcome
D018931:Antineoplastic Agents, Hormonal; D043823:Taxoids; D013629:Tamoxifen; D000077143:Docetaxel; D015251:Epirubicin; D003520:Cyclophosphamide; D005472:Fluorouracil