title: Gemcitabine plus docetaxel versus docetaxel in patients with predominantly human epidermal growth factor receptor 2-negative locally advanced or metastatic breast cancer: a randomized, phase III study by the Danish Breast Cancer Cooperative Group.
abstract: OBJECTIVE
  The objective of this phase III study was to compare the efficacy of gemcitabine plus docetaxel (GD) versus docetaxel in patients with advanced breast cancer.
  
  
  METHODS
  Predominantly human epidermal growth factor receptor 2 (HER2) -negative patients were randomly assigned to gemcitabine (1,000 mg/m(2)) on days 1 and 8 plus docetaxel (75 mg/m(2)) on day 8 or to docetaxel (100 mg/m(2)) on day 1, every 21 days. Patients were untreated or had prior (neo)adjuvant chemotherapy or a single anthracycline-based chemotherapy regimen for metastatic breast cancer. The primary end point was time to progression (TTP), and secondary end points were overall survival (OS), response rate (RR), and toxicity.
  
  
  RESULTS
  A total of 170 patients were allocated to GD, and 167 were allocated to docetaxel. Median TTP on GD was 10.3 months versus 8.3 months on docetaxel (hazard ratio [HR], 0.77; 95% CI, 0.59 to 1.01; log-rank P = .06). The adjusted Cox proportional model for TTP showed a significant difference favoring the combination (HR, 0.68; 95% CI, 0.51 to 0.90; P = .007). However, RR was similar (GD, 36%; docetaxel, 34%), and OS was not different (P = .57). Grades 3 to 4 neutropenia was common (GD, 75%; docetaxel, 69%); infection was reported in 26% and 21% of patients in the GD and docetaxel groups, respectively. Grades 3 to 4 thrombocytopenia was more frequent with GD (GD, 16%; docetaxel, 0.6%), and peripheral neuropathy was higher with docetaxel (GD, 5%; docetaxel, 16%).
  
  
  CONCLUSIONS
  GD compared with docetaxel demonstrated increased TTP in metastatic breast cancer. However, RR and OS were similar. Thus, the addition of gemcitabine failed to demonstrate any clinically meaningful benefit when combined with docetaxel.
authors.affiliation: Herlev Hospital, University of Copenhagen, Copenhagen, Denmark. dornie01@heh.regionh.dk
authors.forename: Dorte Lisbet
authors.initials: DL
authors.lastname: Nielsen
authors.forename: Karsten D
authors.initials: KD
authors.lastname: Bjerre
authors.forename: Erik H
authors.initials: EH
authors.lastname: Jakobsen
authors.forename: Søren
authors.initials: S
authors.lastname: Cold
authors.forename: Lars
authors.initials: L
authors.lastname: Stenbygaard
authors.forename: Peter G
authors.initials: PG
authors.lastname: Sørensen
authors.forename: Claus
authors.initials: C
authors.lastname: Kamby
authors.forename: Susanne
authors.initials: S
authors.lastname: Møller
authors.forename: Charlotte L T
authors.initials: CL
authors.lastname: Jørgensen
authors.forename: Michael
authors.initials: M
authors.lastname: Andersson
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D000077143:Docetaxel; D005260:Female; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis; D016016:Proportional Hazards Models; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis*; D043823:Taxoids / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000093542:Gemcitabine
chemical_list: D003841:Deoxycytidine; D000077143:Docetaxel; D018719:Erb-b2 Receptor Tyrosine Kinases; D043823:Taxoids; D000093542:Gemcitabine; C508053:ERBB2 protein, human