Calcitriol in cancer treatment: From the lab to the clinic

Tomasz M. Beer, Anne Myrthue

    Research output: Contribution to journalShort survey

    134 Scopus citations

    Abstract

    1,25-Dihydroxyvitamin D (calcitriol), the most active metabolite of vitamin D, has significant antineoplastic activity in preclinical models. Several mechanisms of activity have been proposed. These include inhibition of proliferation associated with cell cycle arrest and, in some models, differentiation, reduction in invasiveness and angiogenesis, and induction of apoptosis. Proposed mechanisms differ between tumor models and experimental conditions, and no unifying hypothesis about the mechanism of antineoplastic activity has emerged. Synergistic and/or additive effects with cytotoxic chemotherapy, radiation, and other cancer drugs have been reported. Significantly supraphysiological concentrations of calcitriol are required for antineoplastic effects. Such concentrations are not achievable in patients when calcitriol is dosed daily due to predictable hypercalcemia and hypercalcuria; however, phase I trials have demonstrated that intermittent dosing allows substantial dose escalation and has produced potentially therapeutic peak calcitriol concentrations. Recently, a phase II study reported encouraging levels of activity for the combination of high-dose calcitriol and docetaxel administered on a weekly schedule in patients with androgen-independent prostate cancer. This regimen is now under study in a placebo-controlled randomized trial in androgen-independent prostate cancer and in phase II studies in several other tumor types. Further work is needed to elucidate the molecular mechanisms of antineoplastic activity and optimal clinical applications of calcitriol in cancer.

    Original languageEnglish (US)
    Pages (from-to)373-381
    Number of pages9
    JournalMolecular cancer therapeutics
    Volume3
    Issue number3
    StatePublished - Mar 1 2004

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    ASJC Scopus subject areas

    • Oncology
    • Cancer Research

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