The role of vitamin D in cancer prevention and treatment.

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: 1. Definition of the MTD. 2. Definition of a phase II dose, as a single agent and in combination with cytotoxic agents. 3. Studies to define a biologically optimal dose. 4. Phase II (probably randomized phase II) studies of calcitriol alone and chemotherapy ± calcitriol. 5. Then, randomized phase III trials would be conducted and designed such that the only variable was the administration of calcitriol. Prerequisites 1 to 5 have not been completed for calcitriol. Preclinical data provide considerable rationale for continued development of vitamin D analogue-based cancer therapies. However, design of future studies should be informed by good clinical trials design principles and the mistakes of the past not repeated. Such studies may finally provide compelling data to prove whether or not there is a role for vitamin D analogues in cancer therapy.