High-dose weekly oral calcitriol in patients with a rising PSA after prostatectomy or radiation for prostate carcinoma.
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.
Beer
Tomasz M
TM
Division of Hematology and Medical Oncology, Oregon Health & Science University, Portland 97239-3098, USA. beert@ohsu.edu
Lemmon
Dianne
D
Lowe
Bruce A
BA
Henner
W David
WD
D000368:Aged; D000369:Aged, 80 and over; D002117:Calcitriol / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D002120:Calcium Channel Agonists / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D018450:Disease Progression; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000517:prevention & control*; D017430:Prostate-Specific Antigen / Q000378:metabolism*; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy / Q000601:surgery; D016896:Treatment Outcome
D002120:Calcium Channel Agonists; D017430:Prostate-Specific Antigen; D002117:Calcitriol