title: Randomized, double-blinded phase II evaluation of docetaxel with or without doxercalciferol in patients with metastatic, androgen-independent prostate cancer.
abstract: OBJECTIVE
  Docetaxel is standard of care for androgen-independent prostate cancer (AIPC). Doxercalciferol (1 alpha-hydroxyvitamin D2) had modest activity in phase I/II trials. Preclinical data support combining vitamin D analogues with docetaxel to treat AIPC.
  
  
  METHODS
  Chemotherapy-naive men with metastatic AIPC were randomized 1:1 to receive, on a 4-week cycle, docetaxel (35 mg/m2 i.v., days 1, 8, and 15) with or without doxercalciferol (10 microg orally, days 1-28). The primary end point was prostate-specific antigen (PSA) response. Secondary end points were progression-free survival, overall survival, objective response, and toxicity. Survival was analyzed as intent to treat.
  
  
  RESULTS
  Seventy patients were randomized. Median follow-up was 17.6 months (range, 3.3-45.2). PSA response rate was 46.7% [95% confidence interval (95% CI), 30-64] in the doxercalciferol arm and 39.4% (95% CI, 25-56) with placebo (P = 0.560). Median progression-free survival in the doxercalciferol arm was 6.17 months (95% CI, 4.20-10.7) versus 6.20 months (95% CI, 4.83-9.07) with placebo (P = 0.764). Median overall survival in the doxercalciferol arm was 17.8 months (95% CI, 14.9-23.6) versus 16.4 months (95% CI, 11.9-23.8) with placebo (P = 0.383). Twenty-four patients in the doxercalciferol arm and 23 in the placebo arm were evaluable for objective response. No complete responses were observed. Partial objective response rate was 12.5% with doxercalciferol versus 8.7% with placebo (P = 0.672). Rate of grade > or =3 toxicity was 46% with doxercalciferol versus 42% with placebo (P = 0.785).
  
  
  CONCLUSIONS
  Daily doxercalciferol with weekly docetaxel did not enhance PSA response rate or survival. Toxicity was similar between arms. Despite the disappointing results of this study, other vitamin D analogues remain under active investigation.
authors.affiliation: University of Wisconsin Paul P. Carbone Comprehensive Cancer Center, Madison, WI 53792, USA.
authors.forename: Steven
authors.initials: S
authors.lastname: Attia
authors.forename: Jens
authors.initials: J
authors.lastname: Eickhoff
authors.forename: George
authors.initials: G
authors.lastname: Wilding
authors.forename: Douglas
authors.initials: D
authors.lastname: McNeel
authors.forename: Jules
authors.initials: J
authors.lastname: Blank
authors.forename: Harish
authors.initials: H
authors.lastname: Ahuja
authors.forename: Alcee
authors.initials: A
authors.lastname: Jumonville
authors.forename: Michael
authors.initials: M
authors.lastname: Eastman
authors.forename: Daniel
authors.initials: D
authors.lastname: Shevrin
authors.forename: Michael
authors.initials: M
authors.lastname: Glode
authors.forename: Dona
authors.initials: D
authors.lastname: Alberti
authors.forename: Mary Jane
authors.initials: MJ
authors.lastname: Staab
authors.forename: Dottie
authors.initials: D
authors.lastname: Horvath
authors.forename: Jane
authors.initials: J
authors.lastname: Straus
authors.forename: Rebecca
authors.initials: R
authors.lastname: Marnocha
authors.forename: Glenn
authors.initials: G
authors.lastname: Liu
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000728:Androgens / Q000502:physiology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002118:Calcium / Q000097:blood / Q000652:urine; D000077143:Docetaxel; D004311:Double-Blind Method; D004872:Ergocalciferols / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000401:mortality; D043823:Taxoids / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D000728:Androgens; D004872:Ergocalciferols; D043823:Taxoids; D000077143:Docetaxel; C042533:1 alpha-hydroxyergocalciferol; D002118:Calcium