Calcitriol in the treatment of prostate cancer1

Tomasz M. Beer, Anne Myrthue

Research output: Contribution to journalReview articlepeer-review

47 Scopus citations

Abstract

Calcitriol, the principal active metabolite of vitamin D and a naturally occurring hormone, showed significant antineoplastic activity in pre-clinical models of prostate cancer and many other tumor types. These antineoplastic effects were observed at calcitriol concentrations substantially above the physiological range. While a number of mechanisms of action have been postulated, the induction of apoptosis and inhibition of proliferation have been most extensively reported. These pre-clinical findings motivated several investigators to pursue a series of clinical trials to examine the potential of targeting the vitamin D receptor for cancer treatment using calcitriol. Initial studies tested daily dosing of calcitriol and showed that substantial dose escalation was not feasible due to hypercalciuria and/or hypercalcemia. In contrast, weekly dosing of calcitriol allowed substantial dose escalation without dose-limiting toxicities. Notably, however, the commercially available formulation of calcitriol exhibited non-linear pharmacokinetics at the highest doses tested. While substantially higher concentrations were achieved, the maximum tolerated dose was not established due to this pharmacological limitation. Intermittently-dosed calcitriol was then combined with several antineoplastic agents, including steroids, bisphosphonates and chemotherapeutic agents. The activity seen in a phase II study of weekly calcitriol plus docetaxel was particularly encouraging and led to the development of DN-101, a proprietary formulation designed for cancer treatment. DN-101 in combination with docetaxel is being evaluated in a placebo-controlled randomized clinical trial that has completed accrual.

Original languageEnglish (US)
Pages (from-to)2647-2651
Number of pages5
JournalAnticancer research
Volume26
Issue number4 A
StatePublished - Jul 1 2006

Keywords

  • Calcitriol
  • Prostate cancer
  • Review
  • Vitamin D

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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