Good for the heart, good for the prostate?

IN seeking ways to prevent prostate cancer, medical research has frequently turned to the supermarket. Walk around a grocery store and you’ll find subjects of intense scientific scrutiny in the produce section (vegetables, especially broccoli), condiment aisle (ketchup and tomato sauce) and vitamin shelf (vitamin E and selenium).

In recent years, however, much of the promising research has involved common products found in the pharmacy. Scientists believe that several familiar medications, already used by millions to treat other conditions, may have a new role: helping to lower the toll of prostate cancer, which kills about 30,000 American men each year.

So far, only one treatment has been shown in a large, well-designed study to reduce the risk of prostate cancer: finasteride, a drug widely used to relieve urinary problems. Sold as Proscar, finasteride shrinks an enlarged prostate that can block urine from traveling through the urethra. It works by preventing testosterone from converting into a related chemical -- dihydrotestosterone -- that promotes prostate growth. However, because the drug slows cell division in the prostate, it also reduces the occurrence of cancer-causing mutations.

In a blockbuster study published in 2003 in the New England Journal of Medicine, researchers at the University of Texas followed more than 18,000 men over seven years and found that men who took five milligrams of finasteride every day cut their risk for prostate cancer by 25%.

Despite those encouraging results, doctors have been reluctant to prescribe finasteride to prevent prostate cancer, says Dr. Eric Klein, head of urologic oncology at the Cleveland Clinic’s Glickman Urological Institute. The reason: The Texas study also found that men who took finasteride had a slightly increased risk of developing an aggressive form of prostate cancer -- the type most likely to be fatal.

Klein points out that the risk is very slight -- only about 1%. And he says that even this small risk may be overstated, because finasteride, by shrinking the prostate, may have made aggressive tumors easier to detect. A research paper to be published in the coming months will report that the actual risk of aggressive prostate cancer from finasteride is probably lower than the Texas study suggests, Klein says. “I think the whole community will reassess the use of finasteride after this data is out and we’ll see an interest in prescribing it more widely to prevent prostate cancer.”

Cancer scientists also are interested in the preventive potential of statin drugs such as Lipitor and Zocor. Population studies suggest that men who take statins, which lower cholesterol, have a reduced risk of prostate cancer.

Earlier this year, a group of researchers from Harvard, Johns Hopkins University and the National Cancer Institute presented findings at a medical conference indicating that statin users have half the risk of prostate cancer when compared with nonusers. In another recent study, a team at the Oregon Health & Science University Cancer Institute found that men who have taken statins are 65% less likely to develop prostate cancer than men who never used the drugs.

“The results are intriguing,” says researcher Jackilen Shannon, a professor of public health and preventive medicine at the Oregon Health & Science University School of Medicine, who led the study. But, she cautioned, it’s not yet clear if the statins themselves are responsible for the drop in risk: Men who use statins may have other habits or qualities that are actually doing the protecting. The drugs will have to be studied more before they can be recommended to prevent prostate cancer, Shannon says.

If statins help ward off prostate cancer, scientists have clues as to why. Recent animal research at Children’s Hospital Boston showed that cholesterol gathers in the walls of prostate cancer cells and helps the cells live longer. Another study showed that exposing human prostate cancer cells to statins in a test tube reduces that cholesterol buildup. Sapped of cholesterol, the cancer cells die quickly.

“Prostate cancer might be one of the more sensitive cancers for this type of therapeutic strategy,” says Children’s Hospital researcher Michael Freeman, who led both studies.

Statins may pack a two-fisted punch because they also reduce inflammation, which may be at the root of prostate cancer.

Dr. William G. Nelson, professor of oncology and urology at Johns Hopkins University School of Medicine, explains the link this way: Some men may experience repeated bacterial infections in or near the prostate. In response, the immune system releases inflammatory cells. These kill off the bacteria but may also cause cancerous changes in prostate cells -- a kind of collateral damage.

Another use for aspirin

Armed with this knowledge, scientists around the United States have begun studying whether drugs that relieve inflammation also help prevent prostate cancer.

Their focus is on aspirin and other nonsteroidal anti-inflammatory drugs, or NSAIDs. These block formation of prostaglandins, hormone-like fatty acids that activate inflammation. NSAIDs include nonprescription pain relievers, such as ibuprofen and naproxen, as well as more potent medications, such as Vioxx and Celebrex.

Most studies involving Vioxx and Celebrex two prescription drugs were stopped last year when news broke that they increased the risk of heart attacks. Research involving less potent over-the-counter NSAIDs continues.

So far, the benefits appear modest. For example, in July the American Cancer Society reported a study showing that men who took aspirin or NSAIDs every day for five years decreased their risk for prostate cancer by 18%.

Taking higher doses of NSAIDs may increase their potency against prostate cancer, but the drugs can cause gastrointestinal problems such as stomach ulcers and bleeding, says Dr. David Feldman of the Stanford University School of Medicine.

But maybe there’s a way around that problem. In September, Feldman published a study in the journal Cancer Research showing that it may be possible to boost the effectiveness of NSAIDs against prostate cancer while minimizing stomach risks by pairing them with another prescription drug, calcitriol, which is identical to a form of vitamin D made in the body.

The reason: Vitamin D slows prostate cells from dividing and prevents other changes that can cause cells to turn cancerous. “It makes them behave themselves better,” says Feldman.

Vitamin D also interferes with the activity of prostaglandins. These properties of the vitamin may be why men in the southern United States -- where there is more sunshine to trigger the production of vitamin D in the body -- have lower rates of prostate cancer than men in the north, according to population studies.

Some investigators are studying whether over-the-counter vitamin D supplements would have any effect on prostate cancer. Feldman, meanwhile, has found that combining calcitriol with very small doses of NSAIDs stopped the growth of prostate cancer cells in test tubes. He recently began a trial to study the combination in men.

But for now, real proof that the pair fights the disease in humans is at least several years off.

One day, doctors may prescribe NSAIDs with calcitriol -- or statins, finasteride or some other drug -- to healthy men concerned about prostate cancer.

Until then, men eager to cut their risk can still try the grocery aisles. Nutrition’s power against prostate cancer remains unclear too, but there’s little danger in frequent doses of marinara sauce or broccoli.