The Role of Vitamin D in Cancer Prevention and Treatment
Section snippets
Epidemiology
Epidemiologic studies have noted lower incidence and mortality rates from several cancers in regions with greater solar ultraviolet (UV)-B exposure.3, 4, 5 The potential benefit from sunlight is attributed to vitamin D, because UV light is essential for the cutaneous synthesis of vitamin D.1 The sunlight hypothesis (assuming that sunlight is a surrogate for vitamin D levels in circulation) has been proposed to determine the risk for several cancers6, 7 including colorectal cancer (CRC)3
Mechanisms of the anticancer effects of calcitriol
In addition to the epidemiologic evidence described earlier, data from in vitro studies in cultured malignant cells reveal that calcitriol exerts antiproliferative and prodifferentiating effects; in vivo studies in animal models of cancer demonstrate that calcitriol retards tumor growth.2, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31 Several important mechanisms have been implicated in the anticancer effects of calcitriol. The molecular mediators of these calcitriol actions are currently
Anticancer effects of calcitriol in animal models
Considerable data indicate antitumor effects of vitamin D compounds in in vivo models and calcitriol and calcitriol analogues also potentiate the antitumor actions of many more traditional anticancer agents. In model systems of murine SCC105 and human carcinomas arising in the prostate,46 lung,47 ovary,106 breast,107, 108 bladder,109 pancreas,110 as well as neuroblastoma,111 calcitriol or calcitriol analogues have substantial anticancer effects. Significant inhibition of metastasis is observed
Single-Agent Calcitriol Trials: Phase I Studies and Toxicity
Most anticancer clinical trials of vitamin D analogues have been conducted with calcitriol because it is readily available as an injectable (Calcijex, Abbott Pharmaceuticals, Abbott Park, IL, USA) or oral (Rocaltrol, Hoffman-Roche Laboratories Inc, Nutley, NJ, USA) formulation. As described earlier, preclinical studies indicate that calcitriol has substantial antitumor activity when used in high doses. Most discussions of the role of vitamin D in cancer therapy express the concern that
Summary
Considerable data described in the first part of this review suggest that there is a role for vitamin D in cancer therapy and prevention. Although the preclinical data are persuasive and the epidemiologic data intriguing, no well-designed clinical trial of optimal administration of vitamin D as a cancer therapy has ever been conducted. Had there been the opportunity and insight to develop calcitriol as any other cancer drug, the following studies would have been completed:
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Definition of the MTD
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