title: Phase II to III study comparing doxorubicin and docetaxel with fluorouracil, doxorubicin, and cyclophosphamide as first-line chemotherapy in patients with metastatic breast cancer: results of a Dutch Community Setting Trial for the Clinical Trial Group of the Comprehensive Cancer Centre.
abstract: OBJECTIVE
  To compare the efficacy and safety of doxorubicin and docetaxel (AT) with fluorouracil, doxorubicin, and cyclophosphamide (FAC) as first-line chemotherapy for metastatic breast cancer (MBC).
  
  
  METHODS
  Patients (n = 216) were randomly assigned to either AT (doxorubicin 50 mg/m(2) and docetaxel 75 mg/m2) or FAC (fluorouracil 500 mg/m2, doxorubicin 50 mg/m2, and cyclophosphamide 500 mg/m2); both regimens were administered on day 1, every 3 weeks.
  
  
  RESULTS
  A median number of six cycles was delivered in both arms, with a median relative dose-intensity of more than 98%. Median time to progression (TTP) and median overall survival (OS) were significantly longer for patients on AT compared with FAC (TTP: 8.0 v 6.6 months, respectively; P = .004; and OS: 22.6 v 16.2 months, respectively; P = .019). The overall response rate (ORR) was significantly higher in patients on AT compared with FAC (58% v 37%, respectively; P = .003). The ORR on AT was also higher in patients with visceral disease compared with FAC patients with visceral disease (59% v 36%, respectively; P = .003). There were no differences in grade 3 to 4 neutropenia and infections (AT 89% v FAC 84% and AT 12% v FAC 9%, respectively). Neutropenic fever was more common in AT-treated patients than FAC-treated patients (33% v 9%, respectively; P < .001). Grade 3 to 4 nonhematologic toxicity was infrequent in both arms. Congestive heart failure was observed in 3% and 6% of patients on AT and FAC, respectively.
  
  
  CONCLUSIONS
  In this phase II to III study, AT resulted in a significantly longer TTP and OS and a higher objective ORR than FAC. First-line AT is a valid treatment option for patients with MBC.
authors.affiliation: Department of Medical Oncology, Erasmus University Medical Center, Daniel den Hoed Cancer Center, Rotterdam, the Netherlands. m.bontenbal@erasmusmc.nl
authors.forename: Marijke
authors.initials: M
authors.lastname: Bontenbal
authors.forename: Geert-Jan
authors.initials: GJ
authors.lastname: Creemers
authors.forename: Hans J
authors.initials: HJ
authors.lastname: Braun
authors.forename: Auke C
authors.initials: AC
authors.lastname: de Boer
authors.forename: Jos Th
authors.initials: JT
authors.lastname: Janssen
authors.forename: Rieneke B
authors.initials: RB
authors.lastname: Leys
authors.forename: Jan B
authors.initials: JB
authors.lastname: Ruit
authors.forename: Swan Hoo
authors.initials: SH
authors.lastname: Goey
authors.forename: Paul C
authors.initials: PC
authors.lastname: van der Velden
authors.forename: Leon G
authors.initials: LG
authors.lastname: Kerkhofs
authors.forename: Kristel L
authors.initials: KL
authors.lastname: Schothorst
authors.forename: Paul I
authors.initials: PI
authors.lastname: Schmitz
authors.forename: Hansje J
authors.initials: HJ
authors.lastname: Bokma
authors.forename: Jaap
authors.initials: J
authors.lastname: Verweij
authors.forename: Caroline
authors.initials: C
authors.lastname: Seynaeve
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D003520:Cyclophosphamide / Q000008:administration & dosage; D018450:Disease Progression; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D008875:Middle Aged; D009362:Neoplasm Metastasis; D017239:Paclitaxel / Q000008:administration & dosage; D016019:Survival Analysis
chemical_list: D004317:Doxorubicin; D003520:Cyclophosphamide; D017239:Paclitaxel; D005472:Fluorouracil