Calcitriol in the treatment of prostate cancer1

Tomasz (Tom) Beer, Anne Myrthue

    Research output: Contribution to journalArticle

    40 Citations (Scopus)

    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 2006

    Fingerprint

    Calcitriol
    Prostate
    docetaxel
    Antineoplastic Agents
    Therapeutics
    Hypercalciuria
    Neoplasms
    Calcitriol Receptors
    Maximum Tolerated Dose
    Diphosphonates
    Hypercalcemia
    Vitamin D
    Prostatic Neoplasms
    Randomized Controlled Trials
    Pharmacokinetics
    Steroids
    Placebos
    Research Personnel
    Clinical Trials
    Hormones

    Keywords

    • Calcitriol
    • Prostate cancer
    • Review
    • Vitamin D

    ASJC Scopus subject areas

    • Cancer Research
    • Oncology

    Cite this

    Calcitriol in the treatment of prostate cancer1. / Beer, Tomasz (Tom); Myrthue, Anne.

    In: Anticancer Research, Vol. 26, No. 4 A, 07.2006, p. 2647-2651.

    Research output: Contribution to journalArticle

    Beer, TT & Myrthue, A 2006, 'Calcitriol in the treatment of prostate cancer1', Anticancer Research, vol. 26, no. 4 A, pp. 2647-2651.
    Beer, Tomasz (Tom) ; Myrthue, Anne. / Calcitriol in the treatment of prostate cancer1. In: Anticancer Research. 2006 ; Vol. 26, No. 4 A. pp. 2647-2651.
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