Pills to ward off cancer on the horizon?

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Dec. 29, 2001, 12:52AM

Pills to ward off cancer on the horizon?

Grant to fuel study of chemoprevention

By TODD ACKERMAN

Copyright 2001 Houston Chronicle Medical Writer

Even if you've never heard of chemoprevention, you've undoubtedly used

it.

It's the suntan lotion you slather on to minimize the chances of skin

cancer. And the calcium tablets you pop to slow the progression of

osteoporosis.

But in its strictest sense, in Dr. Waun Ki Hong's laboratory at the

University of Texas M.D. Cancer Center, chemoprevention

involves pills that prevent cancer. There, for the past 15 years, Hong

has investigated how to stop the deadly disease -- mostly lung cancer,

still cancer's No. 1 killer -- before its onset.

" It's not enough to quit smoking, " said Hong, head of M.D. 's

division of cancer medicine. " Though we've seen some improvement in

the treatment of lung cancer in the last decade, there's been little

impact on survival. Chemoprevention is a better strategy: heading off

the disease in those greatest at risk. "

Hong's research team recently received a $10 million grant from the

National Cancer Institute for chemoprevention studies. The grant will

fund a clinical trial and parallel genetic, molecular and

pharmacological studies in the lab.

When the studies are done, Hong says he hopes to have found the

" tamoxifen " for lung cancer. Chemoprevention, a word first used in a

1976 paper, got a boost three years ago when the drug tamoxifen was

found to cut the risk of breast cancer in half.

The challenge is determining which drugs will prevent particular

cancers and which patients will benefit from the drugs.

Hong's clinical trial will involve Celebrex, a drug often prescribed

in the treatment of osteoarthritis but recently found effective in

reducing intestinal polyps in patients with familial adenomatous

polyposis, a precancerous condition that leaves the surface of the

colon essentially carpeted in small polyps.

Hong's trial will enroll patients who smoke or used to smoke one pack

a day for 20 years or two packs a day for 10 years.

Smoking is the cause of 90 percent of the roughly 170,000 new cases of

lung cancer diagnosed every year in the United States, and there are

about 45 million current smokers and 45 million former smokers. Once

lung cancer has spread, the average survival period is eight to l0

months.

Chemoprevention takes advantage of the fact that, in its early stages,

cancer is a slow burn rather than an explosion: It can take years, and

sometimes decades, for a normal cell to transform into a tumor. By

chemoprevention specialists' estimates, more than 22 million

unsuspecting Americans are now experiencing some silent stage of

cancer germination.

Hong, also chairman of M.D. 's department of thoracic/head and

neck medical oncology, became interested in chemoprevention out of

frustration with taking action only after cancer arose -- a philosophy

compared to waiting until people have heart attacks before encouraging

them to lower their cholesterol and start exercising.

Hong fast became one of the field's pioneers, making key discoveries.

He found that ex-smokers still show signs of genetic damage to the

lining of the lungs that puts them at high risk of eventually getting

the disease. He also found that synthetic relatives of vitamin A can

prevent precancerous conditions from progressing to cancer as well as

prevent second tumors from occurring in patients successfully treated

for head and neck cancers. And he identified a biomarker for tracking

the effectiveness of chemoprevention strategies.

Celebrex's great appeal as a lung-cancer preventative is that it

causes few side effects and thus can be taken on a long-term basis.

Synthetic vitamin A, on the other hand, causes a fair amount of

toxicity.

Other projects funded by the NCI grant will examine the molecular

mechanisms of the -2 enzyme, which cancer cells use to propogate

and spread; why some compounds are effective for some patients and not

others; and the molecular and cellular changes in lung tissue and

mechanisms that stimulate cell proliferation.

M.D. researchers also are gathering and analyzing final

results of a recent study with former smokers. One third of the former

smokers took a combination of a synthetic vitamin A derivative and a

synthetic form of vitamin E, a third received a vitamin A derivative

and a third received a placebo.

This is the fourth NCI grant that M.D. has received to

conduct chemoprevention research. In 1995, Hong's multidisciplinary

team was awarded $6 million for the first comprehensive lung cancer

chemoprevention program, and in 1991 and 1996 it received a total of

$14 million to study the biology and chemoprevention of head and neck

cancer. The new grant will be awarded over five years.

M.D. and other institutions across the nation are conducting

chemoprevention trials for cancers of the breast, colon, prostate,

head and neck, bladder and cervix.