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.
Original language | English (US) |
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Pages (from-to) | 1217-1224 |
Number of pages | 8 |
Journal | Cancer |
Volume | 97 |
Issue number | 5 |
DOIs | |
State | Published - Mar 1 2003 |
Externally published | Yes |
Keywords
- 1,25-dihydroxyvitamin D
- 1α,25-dihydroxycholecalciferol
- Calcitriol
- Clinical trial
- Phase II
- Prostate carcinoma
- Prostate specific antigen (PSA)
- Vitamin D
ASJC Scopus subject areas
- Oncology
- Cancer Research