Scientists hope two arthritis drugs may aid in colon-cancer treatment

Scientists are recycling Celebrex and Vioxx, the red-hot inflammation pills taken by tens of millions for arthritis. An unlikely new use is in mind, one more important than soothing throbbing joints. The goal: Prove these ...

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Scientists are recycling Celebrex and Vioxx, the red-hot inflammation pills taken by tens of millions for arthritis. An unlikely new use is in mind, one more important than soothing throbbing joints.

The goal: Prove these medicines prevent cancer and perhaps even help cure it.

While there are good scientific reasons to think they are onto something, the experiments to settle it are not finished, and optimists could be dead wrong. Nevertheless, cancer researchers and pharmaceutical executives entertain fantasies of a breakthrough role for the medicines.

Among them is Dr. Philip Needleman, who has spent more than a decade -- first at Washington University in St. Louis and now at Pharmacia, where he is research director -- developing Celebrex as an arthritis medicine. The 3-year-old drug is the 10th-biggest-selling prescription drug in the United States.

"People ask what gets me juiced," Needleman said. "It's the possibility that in five or 10 years, someone will say, 'Oh, yes. Celebrex. That's also used in arthritis.' "

In a world where people are used to disappointment, hopes run high in industry, government and medical schools that Celebrex and its rivals can be redirected against one of the most feared diseases.

The drugs block production of a chemical called COX-2, which triggers pain and inflammation and also may fuel the growth of cancer, where it often is found in abundance.

The first big test will be in preventing colon cancer, second to lung cancer as a killer. Three big studies involving about 6,000 volunteers will determine if Celebrex and Vioxx stop precancerous growths in the colon. Results should be known within two years.

"If we could reduce the incidence of this disease by half, what an incredible contribution that would be," said Dr. Monica Bertagnolli of Brigham and Women's Hospital in Boston, director of one of the studies. "That's what is driving all of this."

That might be only the start. Experiments on lab animals strongly suggest the arthritis drugs also could help cure cancer, especially if combined with chemotherapy or radiation.

Dr. Andrew Dannenberg, director of cancer prevention at Cornell's Weill Medical College, estimates there may be as many as 100 cancer studies involving these drugs worldwide.

"When in the history of drug development has a drug moved from arthritis to cancer prevention and then been fast-tracked into cancer therapy?" he said. "It's completely unprecedented."

One reason for doctors' willingness to try the drugs is their apparent safety. Celebrex and Vioxx -- known as COX-2 inhibitors -- were designed to be easier on the stomach than aspirin and other inflammation fighters. Their lack of frequent side effects makes them unique in cancer, a field not known for gentle therapies.

A major sponsor of this research is the National Cancer Institute, which oversees Bertagnolli's colon-cancer-prevention study plus many of the smaller treatment experiments with Celebrex.

Dr. Ernest Hawk, the agency's chief of gastrointestinal research, said the government is betting on the drug because of the overlapping lines of evidence -- from epidemiology, animal experiments and more -- that the approach should work.

"What stands out is the weight of the evidence," Hawk said. "I can't think of any class of drugs that have this much going for them, especially in colon cancer. It's the consistency of the story."

Some of the most intriguing evidence comes from big population studies. At least 25 of them, involving about 2 million people, have examined whether colon cancer is less common in people who take aspirin, which works similarly to the new arthritis drugs.

The studies suggest that regular users are about 40 percent less likely than expected to have precancerous polyps or to die from colon cancer.

Results of the first carefully controlled experiment of aspirin in colon cancer will be made public in April. Dr. John Baron of Dartmouth Medical School said it will show aspirin, in fact, does slow the return of precancerous polyps after their removal, although the benefit is modest.

"There may be a tendency for people to hope for a magic bullet and not get it," Baron said. Nevertheless, "the idea that aspirin is effective opens the door for the COX-2 agents," which are safer and may be more powerful, too, as experiments on lab animals seem to show.

In the end, some medical experts say, aspirin may turn out to be the best choice for people at risk of both heart attacks and colon cancer; the COX-2 blockers may make more sense for those worried solely about cancer.

Still, safety is likely to be a concern for the new drugs, too, since even rare side effects could outweigh the benefits when taken lifelong by large numbers of healthy people at average risk of cancer.