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Sulindac Slows Growth of Colon Polyps, May Prevent Colon Cancer

Sulindac Slows Growth of Colon Polyps, May Prevent Colon Cancer

Sulindac sulfone, a nonsteroidal anti-inflammatory drug (NSAID) recently tested in the laboratories of the Arizona Cancer Center, may prove to be an effective colon cancer preventive agent.

Within the last few years, reports the Arizona center, research has suggested that NSAIDs may be effective in preventing colorectal cancer. Sulindac reduces the growth of colon polyps in patients with familial adenomatous polyposis (FAP). Since most colon cancers develop from colon polyps, stopping polyp growth may reduce cancer risk.

"Although sulindac prevents polyp growth, many patients experience side effects, such as upper gastrointestinal (GI) disturbances. Consequently, only about one third of patients can tolerate the drug for prolonged treatment periods," explains David S. Alberts, MD, director of cancer prevention and control. Dr. Alberts worked on the NSAID research with Klaus Brendel, PhD, professor of pharmacology, and Lee Hixson, MD, who since has moved from the University of Arizona.

"Most patients cannot stay on sulindac long enough for it to be an effective chemopreventive agent because this would require daily use, perhaps for life," Dr. Alberts said.

"In looking for a better colon cancer preventive drug, we decided to study derivatives of sulindac, to find the active ingredient responsible for reducing colon polyps. The object was to find a better way to deliver the active ingredient and reduce the side effects."

Several research papers suggested that sulindac's side effects were related to the production of prostaglandins. Sulindac inhibits production of prostaglandins, and many researchers believe that stopping prostaglandin production prevents tumor formation, according to Dr. Alberts.

However, more recent studies conflict with this viewpoint and show that tumors grow even in the absence of prostaglandin. Dr. Alberts' group decided to focus their research on sulindac sulfone, an "inactive" metabolite of sulindac. Previously sulindac sulfone was not shown to be active as an anti-inflammatory agent, and it does not inhibit prostaglandin production.

"Preclinical indications suggest that sulindac sulfone may be as effective as sulindac in reducing colon polyp growth in patients with familial adenomatous polyposis but without the GI side effects. This means patients who can't take sulindac may have a chance to reduce their risk of colon cancer by taking sulindac sulfone," says Dr. Alberts.

The sulindac sulfone study was supported by a grant from Cell Pathways, Inc., of Denver, Colorado, which has licensed the drug from the Technology Transfer Office of the University of Arizona. Cell Pathways also coordinated the clinical trials. The phase I trial, which involved 33 people without FAP, didn't identify any safety problems with the drug, but "we still have a long way to go in the testing process," says Floyd Nicholls, chief executive officer of Cell Pathways. The next study, which will start later this year, will involve patients with FAP.

 
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