Calcitriol and cancer therapy: A missed opportunity

The vitamin D receptor is expressed in most tissues of the body – and the cancers that arise from those tissues. The vitamin D signaling pathway is active in those tissues and cancers. This is at least consistent with the hypothesis that perturbing this signaling may have a favorable effect on the genesis and growth of cancers. Epidemiologic data indicate that vitamin D signaling may be important in the initiation and outcome of a number of types of cancer. Many studies have shown that calcitriol (1,25 dihydroxycholecalciferol) and other vitamin D compounds have antiproliferative, pro-apoptotic, anti-cell migration and antiangiogenic activity in a number of preclinical studies in many different cancer types. Unfortunately, the assessment of the activity of calcitriol or other vitamin D analogues in the treatment of cancer, as single agents or in combination with other anticancer agents has been stymied by the failure to adhere to commonly accepted principles of drug development and clinical trials conduct. •Many studies indicate that vitamin D compounds have cancer prevention and treatment properties in vitro and in vivo cancer models and epidemiologic studies note the association between low vitamin D levels and cancer occurrence and unfavorable outcome.•Many clinical trials in cancer patients have been done to define safety and efficacy of calcitriol and analogues and several trials suggest clinical benefit.•Two randomized trials of calcitriol + chemotherapy (docetaxel) in men with prostate cancer entered >1150 patients.•These trials did not adhere to principles of optimal trial design (choice of optimal dose of drug and balanced randomization) and the failure to execute on these findings is a missed opportunity.