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At 66 years old, Vincent Motyl has the gravelly voice and rumbling laugh of a man who’s spent much of his life in a halo of cigarette smoke.
He’s down to about half a pack a day now, but Motyl didn’t hesitate to enroll when Jonsson Comprehensive Cancer Center at the University of California Los Angeles launched a clinical trial to test whether medication might reduce the odds of developing lung cancer in a smoker or ex-smoker.
It is a simple and compelling idea: If some chemical agent – a common nutrient or a medication already in wide use, for instance – could block, disrupt or reverse the processes that lead to runaway cell growth, then cancer might never need to be cured. It could be prevented.
If only, say experts in the field, the quest for cancer-preventing drugs were so simple, or as readily embraced by physicians and patient advocates as it is by patients like Vincent Motyl. But the effort is an uphill struggle, for several reasons.
Focus and funding are two. Compared with the effort to find drugs to cure and treat cancer, the search for preventive medicine “has been the stepchild” of cancer research, motivating just a small corner of the cancer research community, says Dr. Victor Vogel, a researcher and breast cancer oncologist at the Magee-Womens Hospital/University of Pittsburgh Cancer Institute.
“It’s not sexy, it’s not fancy, and for the pharmaceutical companies, it may not always be very profitable,” Vogel says.
Vast stores of money, brainpower and hope have brought forth drugs capable of extending cancer patients’ survival by months and sometimes years. At the same time, drugs shown to have driven down cancer rates in high-risk populations – ones that have been shown, in studies, to spare people from the ordeal of becoming cancer patients – have been mired in debates over side effects, prevention researchers say.
In recent years, the Food and Drug Administration has approved two medications – the cancer drug tamoxifen and the osteoporosis drug raloxifene – for certain women at high risk of breast cancer.
In 1999, breast cancer activists greeted tamoxifen, the first to be approved, with deep distrust, because it was found to increase the risk of blood clots, uterine abnormalities and cataracts in postmenopausal women.
A year ago, the FDA approved the second, raloxifene, for breast cancer prevention in postmenopausal women at high risk for breast cancer. The agency concluded that the drug could cut the rate of breast cancer in such women between 44 percent and 71 percent, with side-effect risks far lower than tamoxifen.
However, most women at high risk of developing breast cancer who could benefit from drugs such as tamoxifen and raloxifene never have heard of these options, Vogel says.
“We’re trying to find better, safer drugs all the time and trying to overcome both public and physician ignorance about this,” he says. “But you cannot imagine how many people I have to convince.”
But if the search for cancer-preventing medicines is to bear fruit, he says 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 chemotherapy drugs to treat cancer 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.
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 in good health – 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 is poorly defined. Without blood tests or other clear indicators that a patient is likely to 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 clear signs of impending disease.
But even 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 dangers of a cancer-preventing drug should be compared with the very real prospect that the patient will develop incurable cancer.
