title: Hoosier Oncology Group randomized phase II study of docetaxel, vinorelbine, and estramustine in combination in hormone-refractory prostate cancer with pharmacogenetic survival analysis.
abstract: OBJECTIVE
  To determine the safety and efficacy of two docetaxel doublets in hormone-refractory prostate cancer (HRPC) patients and to examine the prognostic role of polymorphisms in host genes important to docetaxel metabolism and transport.
  
  
  METHODS
  Sixty-four chemotherapy-naive patients with HRPC were randomized to docetaxel and vinorelbine (D, 20 mg/m2 i.v. days 1 and 8; V, 25 mg/m2 i.v. days 1 and 8) or docetaxel and estramustine phosphate (D, 60-70 mg/m2 i.v. day 1; E, 280 mg oral thrice daily days 1-5) administered q21d. Primary end point was clinically significant toxicity. A pharmacogenetic analysis of host genes was done in patients who received at least one cycle of docetaxel therapy.
  
  
  RESULTS
  Grade 3/4 toxicity occurred in 15.6% of DV patients and in 28.6% DE patients. Neither arm exceeded the threshold of clinically significant toxicity. In the DV arm, objective response rate was 33%, prostate-specific antigen response rate was 20%, and median survival was 16.2 months. In the DE arm, objective response rate was 67%, prostate-specific antigen response rate was 43%, and median survival was 19.7 months. Pharmacogenetic analyses showed a significant association between survival beyond 15 months and the ABCG2 421 C > A (Q141K) polymorphism compared with the wild-type (C/C) genotype (66% versus 27%; P = 0.05).
  
  
  CONCLUSIONS
  DV and DE doublets are active with a tolerable toxicity profile in patients with HRPC; however, efficacy does not seem superior to standard single-agent docetaxel. The ABCG2 421 C > A (Q141K) polymorphism may be an important predictor of response and survival in HRPC patients treated with docetaxel-based chemotherapy.
authors.affiliation: Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA.
authors.forename: Noah M
authors.initials: NM
authors.lastname: Hahn
authors.forename: Sharon
authors.initials: S
authors.lastname: Marsh
authors.forename: William
authors.initials: W
authors.lastname: Fisher
authors.forename: Robert
authors.initials: R
authors.lastname: Langdon
authors.forename: Robin
authors.initials: R
authors.lastname: Zon
authors.forename: Mark
authors.initials: M
authors.lastname: Browning
authors.forename: Cynthia S
authors.initials: CS
authors.lastname: Johnson
authors.forename: Tiffany J
authors.initials: TJ
authors.lastname: Scott-Horton
authors.forename: Lang
authors.initials: L
authors.lastname: Li
authors.forename: Howard L
authors.initials: HL
authors.lastname: McLeod
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Sweeney
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use* / Q000633:toxicity; D000077143:Docetaxel; D004961:Estramustine / Q000008:administration & dosage / Q000633:toxicity; D006801:Humans; D008297:Male; D008875:Middle Aged; D018579:Patient Selection; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality*; D016019:Survival Analysis; D043823:Taxoids / Q000008:administration & dosage / Q000633:toxicity; D014747:Vinblastine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000633:toxicity; D000077235:Vinorelbine
chemical_list: D043823:Taxoids; D000077143:Docetaxel; D004961:Estramustine; D014747:Vinblastine; D000077235:Vinorelbine