Prostate cancer cell growth halted with calcitriol-NSAID combination

The growth of prostate cancer cells can be halted by combining a form of vitamin D with low doses of a nonsteroidal anti-inflammatory drug, according to results of an in vitro study by researchers at the Stanford (CA) University School of Medicine. The combination reduced prostate cancer cell growth by up to 70%, according to the findings, published in the Sept. 1, 2005 issue of Cancer Research (2005; 65:7917-25).

Senior author David Feldman, MD, had shown in previous studies that calcitriol, the active form of vitamin D, limits the growth of prostate cancer cells. He wanted to see if he could boost calcitrol's effects and lower the dose by using it in conjunction with an NSAID.

"There is great enhancement when the drugs are given together, using what we think is a safe dose in humans," Dr. Feldman said. "It's hard to make an exact comparison, as we are talking about cells in a dish and not a person."

Based on the findings, Dr. Feldman's team has begun a clinical trial in men who have a post-treatment recurrence of prostate cancer. In the current study, the researchers used a cDNA microarray to provide an overview of the genetic changes that occur when prostate cancer cells react to calcitriol. They found that two of the affected genes are critical in the production and breakdown of prostaglandins. Because NSAIDs also block prostaglandin production, the researchers decided to test calcitriol in various combinations with two nonselective NSAIDs, ibuprofen and naproxen.

The group saw a 25% reduction in prostate cell growth using only calcitriol and approximately the same reduction using only ibuprofen and naproxen. But when they combined calcitriol and an NSAID, they saw up to a 70% reduction. This result was obtained using from one-half to one-tenth the concentration required for either of the drugs used alone.