~ Vitamin D Drug Plus NSAID Suppresses Prostate Cancer Cell Growth

The findings of Stanford University School of Medicine researchers published in the September 1 2005 issue of the journal Cancer Research (http://cancerres.aacrjournals.org) show that adding a nonsteroidal anti-inflammatory drug (NSAID) to the active form of vitamin D known as calcitriol reduces the growth of cultured prostate cancer cells by up to 70 percent. The study’s lead author, professor of medicine David Feldman, MD had previously demonstrated that calcitriol limits prostate cancer cell growth.

Dr Feldman’s team tested calcitriol and the NSAIDs naproxen and ibuprofen on prostate cancer cell cultures and found a 25 percent growth reduction associated with each drug. But when both calcitriol and a NSAID were administered in amounts equal to one-tenth to one-half of the quantities used when either drug was tested alone, a 75 percent reduction occurred.

DNA microarray tests revealed two genes affected by calcitriol that are involved in the production and breakdown of prostaglandins. Prostaglandins are hormones that can activate the inflammatory response, which is associated with cancer growth. Nonsteroidal anti-inflammatory drugs work similarly by blocking an enzyme, COX-2, necessary for prostaglandin synthesis.

Dr Feldman commented, "There is great enhancement when the drugs are given together, using what we think is a safe dose in humans."

"NSAIDs have their own risks," Dr Feldman cautioned. "So, we have to be careful even with lower doses and we still need to watch the patients very closely if we intend to keep them on these drugs for extended periods of time. But we are aiming to find doses that are less toxic and far more tolerable for the patient."

Dr Feldman has initiated a clinical trial that is testing the effects of administering naproxen twice daily to prostate cancer patients along with a once per week dose of calcitriol. Once per week dosing avoids the problem of too much calcium in the blood that is associated with taking calcitriol on a daily basis.

The authors "propose that a combination of calcitriol and nonselective NSAIDs might be a useful chemopreventive and/or therapeutic strategy in men with prostate cancer, as it would allow the use of lower concentrations of both drugs, thereby reducing their toxic side effects."


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