High-dose weekly oral calcitriol in patients with a rising PSA after prostatectomy or radiation for prostate carcinoma

Cancer. 2003 Mar 1;97(5):1217-24. doi: 10.1002/cncr.11179.


Background: In preclinical systems, calcitriol, the natural vitamin D receptor (VDR) ligand, has been found to demonstrate antiproliferative effects, although concentrations > 1 nM are required. Unlike daily dosing, weekly administration of oral calcitriol can safely achieve such blood calcitriol concentrations. This study sought to define the long-term toxicity of this regimen and measure its effect on serum prostate specific antigen (PSA) levels in patients with hormone-naïve prostate carcinoma.

Methods: Patients with a rising serum PSA after prostatectomy and/or radiation and no prior systemic therapy for prostate carcinoma recurrence maintained a reduced calcium diet and received calcitriol 0.5 microg/kg orally once each week until a maximum of a four-fold increase in the PSA.

Results: Twenty-two patients received treatment for a median of 10 months (range, 2-25+ months). Treatment was well tolerated with no Grade >or= 3 toxicity and no hypercalcemia or renal calculi. No patient had a PSA response (50% reduction confirmed 4 weeks later). Three patients (14%, 95% CI 0-28%) had confirmed reductions in the PSA ranging from 10% to 47%. Statistically significant increases in the PSA doubling time (PSADT) were seen in three additional patients and no patient had a shorter PSADT after starting treatment. For the entire study population, the median PSADT increased from 7.8 months to 10.3 months (P = 0.03 by Wilcoxon signed rank test).

Conclusions: Weekly high-dose calcitriol was found to be safe. The primary efficacy endpoint of 50% reduction in the serum PSA was not achieved with this therapy. Randomized studies are needed to further examine the impact of this therapy on prostate carcinoma progression.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Calcitriol / administration & dosage*
  • Calcitriol / pharmacokinetics
  • Calcitriol / therapeutic use
  • Calcium Channel Agonists / administration & dosage*
  • Calcium Channel Agonists / pharmacokinetics
  • Calcium Channel Agonists / therapeutic use
  • Disease Progression
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / prevention & control*
  • Prostate-Specific Antigen / metabolism*
  • Prostatectomy
  • Prostatic Neoplasms / drug therapy*
  • Prostatic Neoplasms / radiotherapy
  • Prostatic Neoplasms / surgery
  • Treatment Outcome


  • Calcium Channel Agonists
  • Prostate-Specific Antigen
  • Calcitriol