Date Published: 17 September 2005
Painkiller-vitamin D combination investigated in hope of reducing prostate cancer growth
According to researchers at Stanford University School of Medicine in California (USA), the growth of prostate cancer cells can be halted by combining a form of vitamin D that is currently available only by prescription, with low doses of an over-the-counter painkiller. Researchers found that the specific comination tested reduced prostate cancer cell growth in a laboratory dish by up to 70%, according to data published in the journal Cancer Research, 1 Sept 2005.
The lead author of the study, David Feldman, MD, professor of medicine at Stanford University, has been studying vitamin D for 25 years. He had shown in previous studies that the form of vitamin D, known as calcitriol, limits the growth of prostate cancer cells. (Calcitriol is the the 'active form' of vitamin D, the metabolite that is created in the body after consumption of vitamin D-containing food or exposure to the sun.)
Dr Feldman wanted to find out if he could increase the effects of calcitriol while also reducing the dose required by using it together with another drug. He and his colleagues, including urology professor Donna Peehl, who specializes in developing models of prostate cancer in cultured cells, found that by using calcitriol with nonsteroidal anti-inflammatory drugs, or NSAIDs, they could suppress prostate cancer growth in vitro even more, and with smaller doses, than using either drug alone.
" There is great enhancement when the drugs are given together, using what we think is a safe dose in humans," said Feldman.
" It's hard to make an exact comparison, as we are talking about cells in a dish and not a person."
Based on the outcome of this research, Dr Feldman and his colleagues have already begun a clinical trial in men who have a post-treatment recurrence of prostate cancer. Both calcitriol and nonselective NSAIDs have been used in humans for years, and the safety and risks of these drugs are well known. According to the Centers for Disease Control and Prevention, nearly 30,000 men die annually in the United States from prostate cancer. Among cancers, only lung cancer kills more men. Although prostate cancer is often a slow-growing, noninvasive type of cancer, in some cases a deadly migration of cancer cells invades other parts of the body. The usual treatment for such cases is hormone therapy, but ultimately that treatment does not work for most patients. However, reducing the speed of growth of the prostate cancer cells could buy time for patients before beginning this last-ditch therapy.
Over the course of Dr Feldman's years of vitamin D research, he and others have found that it has several actions that make it useful in cancer therapy. To obtain more information about how calcitriol might reduce or stop tumor growth on a genetic level, the researchers used a cDNA microarray, a tool that provides an overview of the genetic changes that occur when prostate cancer cells react to calcitriol. The researchers discovered that two of the affected genes are critical in the production and breakdown of prostaglandins - hormones that cause a range of physiological effects, including inflammation. Inflammation, in turn, is also associated with cancer growth.
In common with calcitriol, NSAIDs also block prostaglandin production. Therefore it seemed logical to test calcitriol in various combinations with NSAIDs to see if the double whammy could knock out prostate cancer better than either drug alone, explained study leader Dr Jacqueline Moreno.
When the researchers began the study, which was done on cells in culture, they were using selective NSAIDs, such as Vioxx and Celebrex. These drugs specifically target the prostaglandin pathway, reducing the gastrointestinal side effects of the nonselective NSAIDs. But after Vioxx was removed from sale last year due to cardiovascular risks, the researchers changed to using two nonselective NSAIDs, ibuprofen and naproxen, so that the controversy over selective NSAIDs wouldn't adversely affect perceptions of their studies.
The group observed a 25% reduction in prostate cell growth using only calcitriol and about the same reduction using only ibuprofen and naproxen. However, when they combined calcitriol and an NSAID, they saw up to a 70% reduction. This was obtained using from one-half to one-tenth the concentration required for either of the drugs used alone. The group's findings are the basis of a new clinical trial Feldman has begun with oncologist Dr Sandy Srinivas, assistant professor of medicine. Men who have been treated for prostate cancer, but who are experiencing a recurrence, take naproxen twice a day combined with a high, once-weekly dose of calcitriol. Weekly administration of calcitriol avoids a pitfall of earlier studies that used daily dosing: too much calcium in the blood, a condition called hypercalcemia, which can lead to kidney stones.
Dr Feldman's group uses calcitriol for both the cell culture studies and the clinical trial to ensure that enough of the active form of vitamin D is in the patients to be effective. He emphasized that calcitriol is available by prescription only.
" We don't want the patient to think that if they take over-the-counter vitamin D, it will work in the same way," he said.
Source(s): Stanford University, USA.