Double-blinded randomized study of high-dose calcitriol plus docetaxel compared with placebo plus docetaxel in androgen-independent prostate cancer: a report from the ASCENT Investigators

J Clin Oncol. 2007 Feb 20;25(6):669-74. doi: 10.1200/JCO.2006.06.8197.


Purpose: To compare the safety and activity of DN-101, a new high-dose oral formulation of calcitriol designed for cancer therapy, and docetaxel with placebo and docetaxel.

Patients and methods: Patients with progressive metastatic androgen-independent prostate cancer and adequate organ function received weekly docetaxel 36 mg/m2 intravenously for 3 weeks of a 4-week cycle combined with either 45 microg DN-101 or placebo taken orally 1 day before docetaxel. The primary end point was prostate-specific antigen (PSA) response within 6 months of enrollment, defined as a 50% reduction confirmed at least 4 weeks later.

Results: Two hundred fifty patients were randomly assigned. Baseline characteristics were similar in both arms. Within 6 months, PSA responses were seen in 58% in DN-101 patients and 49% in placebo patients (P = .16). Overall, PSA response rates were 63% (DN-101) and 52% (placebo), P = .07. Patients in the DN-101 group had a hazard ratio for death of 0.67 (P = .04) in a multivariate analysis that included baseline hemoglobin and performance status. Median survival has not been reached for the DN-101 arm and is estimated to be 24.5 months using the hazard ratio, compared with 16.4 months for placebo. Grade 3/4 adverse events occurred in 58% of DN-101 patients and in 70% of placebo-treated patients (P = .07). Most common grade 3/4 toxicities for DN-101 versus placebo were neutropenia (10% v 8%), fatigue (8% v 16%), infection (8% v 13%), and hyperglycemia (6% v 12%).

Conclusion: This study suggests that DN-101 treatment was associated with improved survival, but this will require confirmation because survival was not a primary end point. The addition of weekly DN-101 did not increase the toxicity of weekly docetaxel.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Aged
  • Androgens / metabolism*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Biopsy, Needle
  • Calcitriol / administration & dosage*
  • Calcitriol / adverse effects
  • Docetaxel
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Administration Schedule
  • Follow-Up Studies
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Placebos / administration & dosage
  • Prostate-Specific Antigen / blood
  • Prostatic Neoplasms / drug therapy*
  • Prostatic Neoplasms / mortality*
  • Prostatic Neoplasms / pathology
  • Risk Assessment
  • Survival Rate
  • Taxoids / administration & dosage*
  • Taxoids / adverse effects
  • Treatment Outcome


  • Androgens
  • Placebos
  • Taxoids
  • Docetaxel
  • Prostate-Specific Antigen
  • Calcitriol