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Keywords:

  • prostate carcinoma;
  • prostate specific antigen (PSA);
  • clinical trial;
  • Phase II;
  • calcitriol;
  • vitamin D;
  • 1,25-dihydroxyvitamin D;
  • 1α,25-dihydroxycholecalciferol

Abstract

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 μg/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 ≥ 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. Cancer 2003;97:1217–24. © 2003 American Cancer Society.

DOI 10.1002/cncr.11179