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Major Studies Look at the Role of Drugs and Food in Preventing Cancer
"An ounce of prevention...." begins the well-worn saying, but in
the case of cancer it seems a pound of cure is still the best hope.
That may change as researchers study the prospects of preventing cancer with
the aid of "chemopreventive" agents. Just as aggressive treatment of
high blood pressure can prevent stroke, so physicians hope to someday treat
pre-cancerous changes in cells before they progress to full-blown cancer, using
drugs or even compounds found naturally in food.
Acceptable side effects
"The concept of chemoprevention is that treatment of pre-malignant
changes before they progress to malignancy may be done safely and with
acceptable side effects," said Thomas Budd, M.D., director of the
chemoprevention program at The Cleveland Clinic Taussig Cancer Center.
Across the country, major research efforts are underway to study the
prevention of several cancers, especially breast cancer and prostate cancer.
Targeting estrogen to prevent breast cancer
The National Cancer Institute is sponsoring a study at more than 500 centers
nationwide comparing the effects of raloxifene (Evista)—a drug already used to
prevent osteoporosis—and tamoxifen (Nolvadex) in women at risk for breast
cancer. The Study of Tamoxifen and Raloxifene, or STAR, trial will eventually
enroll 22,000 women. Katherine Lee, M.D., and Joseph Crowe, M.D., are
spearheading the Cleveland Clinic’s efforts in the study.
Both drugs are called "selective estrogen receptor modulators" (or
SERMs) for their ability to selectively act on the molecules (known as
receptors) in breast tissue cells that are targets for the hormone estrogen.
Naturally produced by women, estrogen serves many beneficial functions,
including stimulating the proliferation of cells.
However, that function can pose a risk when estrogen stimulates the
proliferation of mutated cells in women at risk for cancer. By treating at-risk
women with drugs that can selectively block the action of estrogen—inhibiting
its ability to stimulate cell proliferation in breast tissue, but not impeding
other vital functions—physicians hope to prevent the development of cancer.
At The Cleveland Clinic and The Ohio State University, Dr. Budd and
colleagues are looking at the effects of another SERM, known as arzoxifene. In
that study, pre-menopausal women with a family history of breast cancer will
receive arzoxifene, tamoxifen or a placebo for six months, Dr. Budd says.
A second study undertaken only at The Cleveland Clinic involves the
preventive effects of perillyl alcohol, a substance found naturally in cherries,
lavender and orange peel. Dr. Budd says the substance already has been found to
be safe when given to adults in single doses.
Biological markers hold a key
In a new round of safety trials, women will be given a daily dose of
perillyl alcohol for three months. During that time, researchers will monitor
side effects, while also looking at "biological markers" to assess how
various doses impact certain biological functions that may be related to the
development of cancer.
Dr. Budd explains that the process by which cells in the body become
cancerous may begin years or even decades before symptoms become apparent. For
this reason, finding discrete biological markers to measure a drug’s
effectiveness is critical to realizing the promise of chemoprevention.
In the study of arzoxifene, for instance, Dr. Budd and his colleagues will be
looking at how the drug impacts production of IGF1, a growth factor in the
bloodstream associated with breast cancer. In addition, they will study the drug’s
effect on breast tissue density, long recognized as a risk factor for breast
cancer.
Antioxidants and prostate cancer
Researchers also are looking at ways to prevent prostate cancer, the most
common form of cancer in American men. The Southwest Oncology Cooperative Group,
a network of more than 280 research institutions, will recruit more than 32,000
men over the age of 55 at 400 study sites to assess the effects selenium and
Vitamin E may have on prostate cancer risk. The study—the Selenium and Vitamin
E Cancer Prevention Trial (SELECT)—is sponsored by the National Cancer
Institute.
Eric Klein, M.D., head of the Section of Urologic Oncology at The Cleveland
Clinic Urological Institute and national study coordinator of the SELECT trial,
explains that selenium and Vitamin E are known "antioxidants," because
they scavenge oxygen-free radicals, which are a byproduct of the body’s
natural oxidation of cells. These free radicals are unstable chemical particles
known to cause mutations in the genetic material of cells, which may in turn
contribute to the development of cancer.
Selenium is a mineral found in grains, meat and fish, while Vitamin E is
plentiful in vegetable oils, sweet potatoes, avocados, nuts, sunflower seeds and
soybeans.
Defining your cancer risk
Both Drs. Klein and Budd caution against using supplements and other
over-the-counter products as preventive agents until their benefits are proved.
Instead, concerned individuals should speak to a physician and try to define
their cancer risk by carefully examining their own and their family’s medical
history. Genetic testing may be helpful in some cases, Dr. Budd says.
"If people are really concerned, they should be open to the idea of
prevention studies," Dr. Budd says. "This is a field that holds
promise but is still experimental."
It is a promise that could save lives and spare many would-be patients the
rigors of expensive and sometimes painful treatment. "Not all cancer is
curable, and treatment has side effects," says Klein. "If you can find
an easy, non-toxic way to prevent cancer, that would be a major public health
benefit."
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