Active vitamin D appears to treat cancer – more studies needed – June 2018

Calcitriol and cancer therapy: A missed opportunity

Bone Reports. online 13 June 2018. https://doi.org/10.1016/j.bonr.2018.06.002
Donald L. Trump,

Highlights

• __Studies in the 1970s and 1980s revealed that vitamin D compounds:
  • had cancer prevention properties in animal models of carcinogen-induced tumors__

•**that the vitamin D receptor was expressed in many tissues and tumors arising from those tissues
•**that vitamin D compounds can slow the growth of tumor cells in vitro
•Numerous epidemiologic studies note the association between low vitamin D levels and cancer occurrence and outcome
•Thousands of 1,25dihydroxycholecalciferol (calcitriol) analogues have been synthesized seeking more effective or less toxic compounds
• Calcitriol suppresses the growth of tumors in vitro and in vivo by numerous mechanisms
• Calcitriol potentiates the anticancer effects of numerous cancer chemotherapy agents
• No analogue has been shown to have superior in vivo or clinical antitumor activity at equitoxic doses compared to calcitriol
• Many clinical trials in cancer patients have been done to define safety and efficacy of calcitriol and analogues
• While several trials suggest clinical benefit, no clearly positive trials have been done
• 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)
• Preclinical data strongly support the role of calcitriol or analogues in cancer therapy
• The failure to execute on these findings is 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.