title: Randomized, open-label phase III trial of docetaxel plus high-dose calcitriol versus docetaxel plus prednisone for patients with castration-resistant prostate cancer.
abstract: OBJECTIVE
  To compare the efficacy and safety of docetaxel plus high-dose calcitriol (DN-101) to docetaxel plus prednisone in an open-label phase III trial.
  
  
  METHODS
  Nine hundred fifty-three men with metastatic castration-resistant prostate cancer (CRPC) were randomly assigned to Androgen-Independent Prostate Cancer Study of Calcitriol Enhancing Taxotere (ASCENT; 45 μg DN-101, 36 mg/m(2) docetaxel, and 24 mg dexamethasone weekly for 3 of every 4 weeks) or control (5 mg prednisone twice daily with 75 mg/m(2) docetaxel and 24 mg dexamethasone every 3 weeks) arms. The primary end point was overall survival (OS), assessed by the Kaplan-Meier method.
  
  
  RESULTS
  At an interim analysis, more deaths were noted in the ASCENT arm, and the trial was halted. The median-follow-up for patients alive at last assessment was 11.7 months. Median OS was 17.8 months (95% CI, 16.0 to 19.5) in the ASCENT arm and 20.2 months (95% CI, 18.8 to 23.0) in the control arm (log-rank P = .002). Survival remained inferior after adjusting for baseline variables (hazard ratio, 1.33; P = .019). The two arms were similar in rates of total and serious adverse events. The most frequent adverse events were GI (reported in 75% of patients), and blood and lymphatic disorders (48%). Docetaxel toxicity leading to dose modification was more frequent in the ASCENT (31%) than in the control arm (15%).
  
  
  CONCLUSIONS
  ASCENT treatment was associated with shorter survival than the control. This difference might be due to either weekly docetaxel dosing, which, in a prior study, showed a trend toward inferior survival compared with an every-3-weeks regimen, or DN-101 therapy.
authors.affiliation: Sidney Kimmel Center for Prostate and Urologic Cancers, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA. scherh@mskcc.org
authors.forename: Howard I
authors.initials: HI
authors.lastname: Scher
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Jia
authors.forename: Kim
authors.initials: K
authors.lastname: Chi
authors.forename: Ronald
authors.initials: R
authors.lastname: de Wit
authors.forename: William R
authors.initials: WR
authors.lastname: Berry
authors.forename: Peter
authors.initials: P
authors.lastname: Albers
authors.forename: Brian
authors.initials: B
authors.lastname: Henick
authors.forename: David
authors.initials: D
authors.lastname: Waterhouse
authors.forename: Dean J
authors.initials: DJ
authors.lastname: Ruether
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Rosen
authors.forename: Anthony A
authors.initials: AA
authors.lastname: Meluch
authors.forename: Luke T
authors.initials: LT
authors.lastname: Nordquist
authors.forename: Peter M
authors.initials: PM
authors.lastname: Venner
authors.forename: Axel
authors.initials: A
authors.lastname: Heidenreich
authors.forename: Luis
authors.initials: L
authors.lastname: Chu
authors.forename: Glenn
authors.initials: G
authors.lastname: Heller
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000401:mortality; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002117:Calcitriol / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000077143:Docetaxel; D019008:Drug Resistance, Neoplasm; D057239:Early Termination of Clinical Trials; D006801:Humans; D008297:Male; D011241:Prednisone / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000401:mortality; D016879:Salvage Therapy / Q000379:methods; D043823:Taxoids / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D043823:Taxoids; D000077143:Docetaxel; D002117:Calcitriol; D011241:Prednisone