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 May 13, 2005
Painkillers May Protect Against Colon Cancer
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By Amanda Gardner, HealthDay Reporter

MONDAY, April 18 (HealthDay News) -- Ever since Vioxx and its sister drugs hit the headlines, attention has been focused on the unintended cardiovascular risks of nonsteroidal anti-inflammatory drugs (NSAIDs).

Now, however, some of that attention is being refocused on the potential anti-cancer properties of these drugs.

Two studies presented April 18 at the American Association for Cancer Research annual meeting, in Anaheim, Calif., provide evidence that the drugs may have some benefit against colon cancer.

The first study found that low doses of Celebrex, an NSAID that is part of the cox-2 drug family, and Lipitor, a statin drug normally used to lower cholesterol levels, were more effective when given in tandem against colon cancer in lab animals than higher doses of either drug on its own.

"Ninety percent of the tumors were suppressed, which is amazing," said study author Dr. Bandaru Reddy, a research professor at Rutgers University's School of Pharmacy, in Piscataway, N.J.

The combination also had fewer side effects than either drug separately.

A second study found that Celebrex altered the genes of people at risk for colorectal cancer. It's possible that these changes indicate a preventive effect, although the researchers still don't know for certain.

Celebrex is the only cox-2 inhibitor left on the U.S. market since Vioxx and Bextra were withdrawn, following reports of heightened cardiovascular risks. Cox-2 inhibitors are a class of NSAID pain relievers that are safer on the stomach.

"There's strong epidemiological and experimental evidence that NSAIDs, including aspirin, can reduce the risk of colon cancer," Reddy said. "There is also good evidence that cox-2 inhibitors can prevent carcinoma in a pre-clinical model, but toxicity [side effects] was a major concern because they're using high doses."

In Reddy's experiment, rats received the equivalent of 120 milligrams a day of Celebrex and 40 milligrams a day of Lipitor. These animals had a 95 percent reduction in invasive and non-invasive cancers, compared to the control group.

Celebrex on its own reduced the incidence and number of colon tumors by 80 percent. Lipitor reduced tumor incidence by 31 percent to 41 percent.

This somewhat paradoxical effect of greater efficacy and lower toxicity can be explained by the fact that the drug combination targets more than one gene, Reddy said.

"These two components work together synergistically," Reddy explained.

In the second study, researchers looked at gene expression profiles in people at risk for colon cancer at the beginning of the trial and then again after taking Celebrex for one year. None of the participants had colon cancer at the outset.

"The result was that we could indeed see that there was a difference in patterns of gene expression in the normal colonic mucosa in those individuals who had received Celebrex," said study author Dr. Ilan Kirsch, chief of the genetics branch at the Center for Cancer Research at the National Cancer Institute.

The significance of the findings is not yet clear, although the genes implicated are associated with processes of inflammation and proliferation.

"In general, it appears that the pathways that instigate inflammation were kind of tuned down," Kirsch said. "Similarly, pathways that stimulate proliferation were kind of tuned down. In general, in the progression of normal cell to cancerous ones, you begin to see more proliferation and inflammation. It's consistent with a risk-reducing effect, which is not to say that we really know."

More information

For more on colorectal cancer, visit the American Cancer Society (www.cancer.org ).

SOURCES: Bandaru Reddy, D.V.M., Ph.D., research professor, School of Pharmacy, Rutgers University, Piscataway, N.J.; Ilan Kirsch, M.D., chief, genetics branch, Center for Cancer Research, National Cancer Institute, Bethesda, Md.; April 18, 2005, presentations, American Association for Cancer Research annual meeting, Anaheim, Calif.

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