title: Fluorouracil, doxorubicin, and cyclophosphamide (FAC) versus FAC followed by weekly paclitaxel as adjuvant therapy for high-risk, node-negative breast cancer: results from the GEICAM/2003-02 study.
abstract: OBJECTIVE
  Adding taxanes to anthracycline-based adjuvant therapy improves survival outcomes of patients with node-positive breast cancer (BC). Currently, however, most patients with BC are node negative at diagnosis. The only pure node-negative study (Spanish Breast Cancer Research Group 9805) reported so far showed a docetaxel benefit but significant toxicity. Here we tested the efficacy and safety of weekly paclitaxel (wP) in node-negative patients, which is yet to be established.
  
  
  METHODS
  Patients with BC having T1-T3/N0 tumors and at least one high-risk factor for recurrence (according to St. Gallen 1998 criteria) were eligible. After primary surgery, 1,925 patients were randomly assigned to receive fluorouracil, doxorubicin, and cyclophosphamide (FAC) × 6 or FAC × 4 followed by wP × 8 (FAC-wP). The primary end point was disease-free survival (DFS) after a median follow-up of 5 years. Secondary end points included toxicity and overall survival.
  
  
  RESULTS
  After a median follow-up of 63.3 months, 93% and 90.3% of patients receiving FAC-wP or FAC regimens, respectively, remained disease free (hazard ratio [HR], 0.73; 95% CI, 0.54 to 0.99; log-rank P = .04). Thirty-one patients receiving FAC-wP versus 40 patients receiving FAC died (one and seven from cardiovascular diseases, respectively; HR, 0.79; 95% CI, 0.49 to 1.26; log-rank P = .31). The most relevant grade 3 and 4 adverse events in the FAC-wP versus the FAC arm were febrile neutropenia (2.7% v 3.6%), fatigue (7.9% v 3.4%), and sensory neuropathy (5.5% v 0%).
  
  
  CONCLUSIONS
  For patients with high-risk node-negative BC, the adjuvant FAC-wP regimen was associated with a small but significant improvement in DFS compared with FAC therapy, in addition to manageable toxicity, especially regarding long-term cardiac effects.
authors.affiliation: Instituto de Investigación Sanitaria Gregorio Marañon, Universidad Complutense, Dr. Esquerdo 46, Madrid 28009, Spain. mmartin@geicam.org
authors.forename: Miguel
authors.initials: M
authors.lastname: Martín
authors.forename: Amparo
authors.initials: A
authors.lastname: Ruiz
authors.forename: Manuel
authors.initials: M
authors.lastname: Ruiz Borrego
authors.forename: Agustí
authors.initials: A
authors.lastname: Barnadas
authors.forename: Sonia
authors.initials: S
authors.lastname: González
authors.forename: Lourdes
authors.initials: L
authors.lastname: Calvo
authors.forename: Mireia
authors.initials: M
authors.lastname: Margelí Vila
authors.forename: Antonio
authors.initials: A
authors.lastname: Antón
authors.forename: Alvaro
authors.initials: A
authors.lastname: Rodríguez-Lescure
authors.forename: Miguel Angel
authors.initials: MA
authors.lastname: Seguí-Palmer
authors.forename: Montserrat
authors.initials: M
authors.lastname: Muñoz-Mateu
authors.forename: Joan
authors.initials: J
authors.lastname: Dorca Ribugent
authors.forename: José Manuel
authors.initials: JM
authors.lastname: López-Vega
authors.forename: Carlos
authors.initials: C
authors.lastname: Jara
authors.forename: Enrique
authors.initials: E
authors.lastname: Espinosa
authors.forename: César
authors.initials: C
authors.lastname: Mendiola Fernández
authors.forename: Raquel
authors.initials: R
authors.lastname: Andrés
authors.forename: Nuria
authors.initials: N
authors.lastname: Ribelles
authors.forename: Arrate
authors.initials: A
authors.lastname: Plazaola
authors.forename: Pedro
authors.initials: P
authors.lastname: Sánchez-Rovira
authors.forename: Javier
authors.initials: J
authors.lastname: Salvador Bofill
authors.forename: Carmen
authors.initials: C
authors.lastname: Crespo
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Carabantes
authors.forename: Sonia
authors.initials: S
authors.lastname: Servitja
authors.forename: José Ignacio
authors.initials: JI
authors.lastname: Chacón
authors.forename: César A
authors.initials: CA
authors.lastname: Rodríguez
authors.forename: Blanca
authors.initials: B
authors.lastname: Hernando
authors.forename: Isabel
authors.initials: I
authors.lastname: Álvarez
authors.forename: Eva
authors.initials: E
authors.lastname: Carrasco
authors.forename: Ana
authors.initials: A
authors.lastname: Lluch
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality* / Q000473:pathology / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D016001:Confidence Intervals; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D005500:Follow-Up Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D008198:Lymph Nodes / Q000473:pathology; D008408:Mastectomy / Q000379:methods; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000473:pathology; D009364:Neoplasm Recurrence, Local / Q000401:mortality* / Q000473:pathology / Q000628:therapy; D009367:Neoplasm Staging; D017239:Paclitaxel / Q000008:administration & dosage* / Q000009:adverse effects; D016016:Proportional Hazards Models; D018570:Risk Assessment; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D004317:Doxorubicin; D003520:Cyclophosphamide; D017239:Paclitaxel; D005472:Fluorouracil