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Rationale for the development and current status of calcitriol in androgen-independent prostate cancer

Tomasz M Beer1, Anne Myrthue, Kristine M Eilers

  • 1Division of Hematology and Medical Oncology, Oregon Health and Science University, Mail Code CR-145, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA. beert@ohsu.edu

World Journal of Urology
|January 26, 2005
PubMed

Insights

Calcitriol, a vitamin D metabolite, shows anti-cancer effects in prostate cancer models. Intermittent dosing allows higher, potentially synergistic, doses when combined with chemotherapy agents like docetaxel.

Area of Science:

  • Oncology
  • Endocrinology
  • Pharmacology

Background:

  • Calcitriol, the active form of vitamin D, exhibits significant antineoplastic properties against various cancers, including prostate cancer.
  • Its mechanisms involve inhibiting cell proliferation, inducing apoptosis, and reducing tumor invasiveness and angiogenesis.
  • Preclinical studies indicate calcitriol may synergize with prostate cancer therapies like dexamethasone and cytotoxic agents.

Purpose of the Study:

  • To evaluate the antineoplastic activity of calcitriol in prostate cancer.
  • To explore the synergistic potential of calcitriol in combination with standard prostate cancer treatments.
  • To assess the feasibility of dose escalation through intermittent administration for achieving therapeutic concentrations.

Main Methods:

  • Pre-clinical models of prostate cancer were utilized to investigate calcitriol's effects.
  • Studies examined the impact of calcitriol on cell proliferation, cell cycle, apoptosis, invasiveness, and angiogenesis.
  • Combination studies explored additive or synergistic effects with relevant chemotherapeutic agents and dexamethasone.
  • Phase II and ongoing randomized placebo-controlled trials assess intermittent calcitriol combined with docetaxel.

Main Results:

  • Calcitriol demonstrated significant antineoplastic activity in preclinical prostate cancer models.
  • Synergistic or additive effects were observed when calcitriol was combined with agents like docetaxel and dexamethasone.
  • Intermittent dosing strategies enabled dose escalation beyond safe conventional daily administration levels.
  • A Phase II study reported encouraging outcomes for calcitriol combined with weekly docetaxel.

Conclusions:

  • Calcitriol possesses potent antineoplastic activity relevant to prostate cancer treatment.
  • Intermittent administration is a viable strategy for achieving higher, potentially synergistic, therapeutic doses.
  • Combination therapy with calcitriol and agents like docetaxel shows promise, pending results from ongoing clinical trials.

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