title: Phase III study of gemcitabine plus docetaxel compared with capecitabine plus docetaxel for anthracycline-pretreated patients with metastatic breast cancer.
abstract: OBJECTIVE
  Patients with metastatic breast cancer who are pretreated with anthracyclines frequently receive taxane-based combinations. This phase III study compared the efficacy and safety of gemcitabine-docetaxel (GD) with capecitabine-docetaxel (CD) in advanced breast cancer.
  
  
  METHODS
  Patients were randomly assigned to GD (G 1,000 mg/m(2) days 1 and 8; D 75 mg/m(2) day 1) or CD (C 1,250 mg/m(2) twice daily days 1 through 14; D 75 mg/m(2) day 1) every 21 days. Comparison of progression-free survival (PFS) was the primary objective.
  
  
  RESULTS
  Patient characteristics were balanced between arms (N = 305). Median PFS was 8.05 months (95% CI, 6.60 to 8.71) for GD and 7.98 (95% CI, 6.93 to 8.77) for CD (log-rank P = .121). Overall response rate (ORR) was 32% in both arms, and overall survival (OS) was not different between arms (P = .983). Time to treatment failure (TTF; defined as discontinuation, progressive disease, death as a result of any cause, or the start of a new anticancer therapy) was superior in the GD arm (P = .059). Hematologic toxicity was similar in both arms, except for grades 3 to 4 leukopenia (GD, 78%; CD, 66%; P = .025) and transfusions (GD, 17%; CD, 7%; P = .0051). Grades 3 to 4 diarrhea, mucositis, and hand-and-foot syndrome were significantly higher in the CD arm. Fewer patients in the GD arm discontinued because of drug-related adverse events (13% v 27% in CD; P = .002).
  
  
  CONCLUSIONS
  No difference was observed between GD and CD arms in PFS, ORR, and OS. TTF was longer in the GD arm. These findings, combined with a nonhematologic toxicity profile that favors GD over approved doses of CD, suggest that gemcitabine may be a better option than capecitabine in combination with docetaxel in this clinical setting.
authors.affiliation: Nottingham University Hospital, City Campus, Nottingham, UK. steve.chan@nuh.nhs.uk
authors.forename: Stephen
authors.initials: S
authors.lastname: Chan
authors.forename: Gilles
authors.initials: G
authors.lastname: Romieu
authors.forename: Jens
authors.initials: J
authors.lastname: Huober
authors.forename: Thierry
authors.initials: T
authors.lastname: Delozier
authors.forename: Michele
authors.initials: M
authors.lastname: Tubiana-Hulin
authors.forename: Andreas
authors.initials: A
authors.lastname: Schneeweiss
authors.forename: Ana
authors.initials: A
authors.lastname: Lluch
authors.forename: Antonio
authors.initials: A
authors.lastname: Llombart
authors.forename: Andreas
authors.initials: A
authors.lastname: du Bois
authors.forename: Rolf
authors.initials: R
authors.lastname: Kreienberg
authors.forename: Jose Ignacio
authors.initials: JI
authors.lastname: Mayordomo
authors.forename: Antonio
authors.initials: A
authors.lastname: Antón
authors.forename: Mark
authors.initials: M
authors.lastname: Harrison
authors.forename: Alison
authors.initials: A
authors.lastname: Jones
authors.forename: Eva
authors.initials: E
authors.lastname: Carrasco
authors.forename: A Thareau
authors.initials: AT
authors.lastname: Vaury
authors.forename: Bente
authors.initials: B
authors.lastname: Frimodt-Moller
authors.forename: Pierre
authors.initials: P
authors.lastname: Fumoleau
mesh_terms: D000328:Adult; D000368:Aged; D018943:Anthracyclines / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000556:secondary; D000069287:Capecitabine; D003131:Combined Modality Therapy; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000077143:Docetaxel; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D008875:Middle Aged; D016019:Survival Analysis; D043823:Taxoids / Q000008:administration & dosage; D000093542:Gemcitabine
chemical_list: D018943:Anthracyclines; D043823:Taxoids; D003841:Deoxycytidine; D000077143:Docetaxel; D000069287:Capecitabine; D005472:Fluorouracil; D000093542:Gemcitabine