• 3/18/2004
  • Irvine, Ca.
  • Linda Marsa
  • LA Times

Because the early signs of oral cancer — white spots or red areas in the mouth —are painless and difficult to detect, diagnosis usually occurs only after the disease has spread to the lymph nodes in the neck. Consequently, patients often need aggressive, disfiguring surgical treatments. Half of those diagnosed will die of the disease. “Mortality rates haven’t changed in 40 years because we don’t have any good treatments beyond surgery, and no way of preventing cancers from returning,” says Dr. Frank L. Meyskens Jr., an oncologist at the Chao Family Comprehensive Cancer Center at the UC Irvine Medical Center.

But Meyskens and other scientists are testing a soy-derived experimental treatment that could reduce this deadly toll — by stopping oral cancers from developing in the first place. If the drug proves effective, it may be used routinely to protect against oral cancer in people who are at increased risk.
“Survival rates haven’t improved much over the years, so a preventive agent would be very useful,” says Sol Silverman, a professor of oral medicine at UC San Francisco Medical School and spokesman for the American Dental Assn. in Chicago. “This approach seems promising.” About 30,000 Americans are diagnosed with oral cancer each year, and only 57% survive more than five years.

Tobacco use is the culprit behind about 75% of oral cancer cases, and alcohol also is a major contributing factor. Oral cancer is the leading cancer among men in India, and incidence rates can be as high as 40% in Southeast Asia, where people chew betel nuts, which contain lye, or tobacco laced with lime, both of which irritate mouth tissue. The soy derivative, known as the Bowman-Birk inhibitor, seems to work by blocking the production of certain enzymes that can prompt cells to turn cancerous. (Scientists had noticed that people whose diets were rich in soybean products had a lower incidence of cancer, which prompted studies of soy’s chemical constituents.)
A 1999 study of 32 patients with leukoplakia, a potentially precancerous disease of the mouth in which white patches form on the tongue and inside the mouth, was promising.

Volunteers took a twice-daily dose of the soy derivative in a mouth rinse, which they swished around their mouths and then swallowed. After a month, there was an overall 24.2% decrease in lesion size. “In a couple of patients the lesions were completely gone, which we found very encouraging for such a short study,” Meyskens says.

Researchers are now in the midst of a longer study of 130 patients. Half receive a placebo, while the remainder take the drug for as long as two years to determine whether it can completely eradicate lesions and protect against recurrences of the precancerous condition. If it works, the next step is to test it on people with head and neck cancers, which have high rates of recurrence. “Right now, these patients have no preventive options,” Meyskens says.

About the chemical

The Bowman-Birk inhibitor is a very versatile chemical, says Ann R. Kennedy, a radiation oncologist who has studied the soy derivative for more than 30 years. In addition to potentially guarding against cancer, this component of soy also may reduce inflammation and prevent muscles from weakening from disuse.
The compound already has shown promise in clinical trials for reducing colon inflammation in people with ulcerative colitis and easing swelling in patients with enlarged prostates, which is a common condition in older men. In the near future, scientists plan tests of the chemical’s ability to prevent muscle atrophy in multiple sclerosis sufferers and in people with spinal cord injuries who are bedridden.

“When we first studied the Bowman-Birk inhibitor, we observed that it stopped the malignant transformation of cells,” says Kennedy, a professor of research oncology at the University of Pennsylvania School of Medicine. “But now we’ve discovered that it can be useful in many other areas.”