Randomized phase 3 trial of fluorouracil, epirubicin, and cyclophosphamide alone or followed by Paclitaxel for early breast cancer.
BACKGROUND
Taxanes are among the most active drugs for the treatment of metastatic breast cancer, and, as a consequence, they have also been studied in the adjuvant setting.


METHODS
After breast cancer surgery, women with lymph node-positive disease were randomly assigned to treatment with fluorouracil, epirubicin, and cyclophosphamide (FEC) or with FEC followed by weekly paclitaxel (FEC-P). The primary endpoint of study-5-year disease-free survival (DFS)-was assessed by Kaplan-Meier analysis. Secondary endpoints included overall survival and analysis of the prognostic and predictive value of clinical and molecular (hormone receptors by immunohistochemistry and HER2 by fluorescence in situ hybridization) markers. Associations and interactions were assessed with a multivariable Cox proportional hazards model for DFS for the following covariates: age, menopausal status, tumor size, lymph node status, type of chemotherapy, tumor size, positive lymph nodes, HER2 status, and hormone receptor status. All statistical tests were two-sided.


RESULTS
Among the 1246 eligible patients, estimated rates of DFS at 5 years were 78.5% in the FEC-P arm and 72.1% in the FEC arm (difference = 6.4%, 95% confidence interval [CI] = 1.6% to 11.2%; P = .006). FEC-P treatment was associated with a 23% reduction in the risk of relapse compared with FEC treatment (146 relapses in the 614 patients in the FEC-P arm vs 193 relapses in the 632 patients in the FEC arm, hazard ratio [HR] = 0.77, 95% CI = 0.62 to 0.95; P = .022) and a 22% reduction in the risk of death (73 and 95 deaths, respectively, HR = 0.78, 95% CI = 0.57 to 1.06; P = .110). Among the 928 patients for whom tumor samples were centrally analyzed, type of chemotherapy (FEC vs FEC-P) (P = .017), number of involved axillary lymph nodes (P < .001), tumor size (P = .020), hormone receptor status (P = .004), and HER2 status (P = .006) were all associated with DFS. We found no statistically significant interaction between HER2 status and paclitaxel treatment or between hormone receptor status and paclitaxel treatment.


CONCLUSIONS
Among patients with operable breast cancer, FEC-P treatment statistically significantly reduced the risk of relapse compared with FEC as adjuvant therapy.
Martín
Miguel
M
Servicio de Oncologia Medica, Hospital Universitario San Carlos, Ciudad Universitaria s/n, 28040 Madrid, Spain. mmartin@geicam.org
Rodríguez-Lescure
Alvaro
A
Ruiz
Amparo
A
Alba
Emilio
E
Calvo
Lourdes
L
Ruiz-Borrego
Manuel
M
Munárriz
Blanca
B
Rodríguez
César A
CA
Crespo
Carmen
C
de Alava
Enrique
E
López García-Asenjo
José Antonio
JA
Guitián
María Dolores
MD
Almenar
Sergio
S
González-Palacios
Jesús Fernando
JF
Vera
Francisco
F
Palacios
José
J
Ramos
Manuel
M
Gracia Marco
Jose Manuel
JM
Lluch
Ana
A
Alvarez
Isabel
I
Seguí
Miguel Angel
MA
Mayordomo
José Ignacio
JI
Antón
Antonio
A
Baena
José Manuel
JM
Plazaola
Arrate
A
Modolell
Alfonso
A
Pelegrí
Amadeu
A
Mel
Jose Ramón
JR
Aranda
Enrique
E
Adrover
Encarna
E
Alvarez
José Valero
JV
García Puche
José Luis
JL
Sánchez-Rovira
Pedro
P
Gonzalez
Sonia
S
López-Vega
José Manuel
JM
D000328:Adult; D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000473:pathology*; D018270:Carcinoma, Ductal, Breast / Q000188:drug therapy / Q000556:secondary; D018275:Carcinoma, Lobular / Q000188:drug therapy / Q000556:secondary; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D007262:Infusions, Intravenous; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D009367:Neoplasm Staging; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis; D016896:Treatment Outcome
D000972:Antineoplastic Agents, Phytogenic; D014408:Biomarkers, Tumor; D003520:Cyclophosphamide; D015251:Epirubicin; D005472:Fluorouracil; D017239:Paclitaxel; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C508053:ERBB2 protein, human