Calcitriol - promising chemopreventive agent that may prevent prostate cancer

The active metabolite of vitamin D, calcitriol, and other vitamin D analogs are promising chemopreventive agents that may prevent prostate cancer, according to a study presented today at the American Association for Cancer Research's 4th annual Frontiers in Cancer Prevention Research meeting in Baltimore.

Researchers from Roswell Park Cancer Institute conducted both in vitro (outside the body) and in vivo (inside the body) studies to determine the effects of calcitriol and the analogs, QW-1624-F2-2 and paricalcitol, on the prevention of prostate cancer.

Calcitriol is the active metabolite of vitamin D, and is used clinically to treat a variety of disorders, including recent clinical trials for established cancer. A major obstacle to clinical use of calcitriol is dose-limiting hypercalcemia (abnormally high concentration of calcium in the blood). QW, developed at Johns Hopkins University and paricalcitol (Zemplar) have been shown to reduce parathyroid hormone levels (which regulate the metabolism of calcium and phosphorus in the body).

The researchers then studied the effects of calcitriol and QW on the prevention of androgen-dependent prostate cancer in the transgenic adenocarcinoma of mouse prostate (TRAMP) model, which develops prostate cancer as the mice age. Both calcitriol and QW slowed the progression of prostate cancer in intact TRAMP mice after 14 weeks of treatment as indicated by decreased reproductive tract and prostate weight. In addition, chronic treatment of mice with calcitriol markedly reduced tumor burden, although side effects were seen in some mice.

The effect of calcitriol and QW on hormone refractory prostate cancer was also investigated, using castrated TRAMP mice. Results showed that vitamin D had no effect on disease progression in castrated mice as measured by reproductive tract and prostate weight.

"Our pre-clinical data using the TRAMP mouse model, which mimics human prostate cancer, suggests that calcitriol and QW-1624-F2-2 are promising for prevention of androgen-dependent prostate cancer progression. Further studies are under way in our laboratory to better understand how these agents prevent prostate cancer," said Adebusola Alagbala of Roswell Park Cancer Institute and lead author of the study. The studies, funded by the National Institutes of Health, were conducted in the laboratory of Dr. Barbara A. Foster at Roswell Park Cancer Institute.