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Prevention: Is it just the right drug away?

October 20, 2008|Melissa Healy | Times Staff Writer

To be sure, agents that seem promising may later fall by the wayside. A combination of vitamin A and beta-carotene was one of the cancer chemoprevention community's most spectacular disappointments when, in studies completed in the 1990s, the regimen not only failed to reduce lung cancer rates but in fact boosted them among male smokers.

Still, many common nutrients -- including beta-carotene -- remain under investigation as potential cancer-blockers. Folic acid, vitamin D, selenium, lycopene, the spice ingredient curcumin, green tea and resveratrol, a compound found largely in the skins of red grapes, all are being tested in clinical trials.

The wide variety of chemicals that might help prevent cancer reflects the range of processes that go wrong when cells turn malignant. Dr. Michael Sporn, a professor of medicine and pharmacology at Dartmouth Medical School, says that different agents may disrupt the processes leading to cancer at different stages. It may prove that combinations of agents will be the most powerful, he says.

But if the search for cancer-preventing medicines is to bear fruit, he thinks that cancer researchers, clinicians and the government's drug-safety regulators will have to rethink their attitudes about risk, reward and medicine.

"The notion of preventing cancer is intuitively obvious to everyone but the oncology community," Sporn says.

In some ways, cancer-prevention drugs have the deck stacked against them, experts say. Most cancer chemotherapy drugs are known to come with horrific side effects. But the balance of risk and benefit often looks good anyway: Patients and their physicians usually calculate that likely side effects compare favorably with the far worse prospect of letting cancer run its course.


Risk vs. benefit

In prevention, the calculation of risk and benefit is much more complex. What doctor would ask a patient whose future risk for cancer is uncertain -- and who by all appearances is currently well -- to take a cancer-prevention drug with recognized side effects such as liver toxicity or increased risk of stroke or heart attack?

Sporn calls this the "long uphill battle" that advocates of cancer chemoprevention face. And it is a battle made harder by the fact that a person's cancer risk -- in most cases a complex interaction between genetic predisposition, environmental exposures and pure bad luck -- is poorly defined. Without blood tests or other clear indicators that a patient will likely develop cancer, physicians have shown they are reluctant to prescribe drugs for prevention, even where their benefits have been shown.

The FDA, too, remains wary of the use of drugs to treat patients without clearer signs of impending disease.

But though cancer experts have not found easy markers of cancer risk, Sporn says, there are plenty of patients whose polyps, moles, family history or chromosomes offer ample warning of trouble ahead.

For such people, he says, the risk profile of a potential cancer-preventing drug really should be compared to the very real prospect that the patient will develop a life-threatening cancer and that oncology in many cases will have little prospect of a cure to offer him.


Rethinking cancer

Advocates of cancer-prevention research see a model for the way things should be in the treatment of cardiovascular disease. In that field, primary care doctors and heart specialists, armed with medications to lower cholesterol and blood pressure, have jumped wholeheartedly into the prevention of heart attacks and strokes. And even as they debate how to measure a patient's future risk, the field has agreed on blood pressure levels and cholesterol measures that are "markers" for heart disease and stroke and has used those to guide medication decisions.

The search for equally reliable indicators of cancer risk remains in its infancy. But doctors who treat cancer and the organs it invades should follow the cardiovascular model, says Dr. Leslie Ford, associate director for clinical research at the National Cancer Institute's Division of Cancer Prevention.

"I challenge oncologists to think differently -- to find people with risk factors for cancer and think about prevention," Ford says. "They haven't gotten there. It's not where the money is . . . and primary care physicians are overcome with other problems. It's a real challenge, but we're plugging along. I'm cautiously optimistic."



On the Web

The hurdles are high for cancer-prevention drugs, as shown by the story of celecoxib, also known as Celebrex. Read about it at

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