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, researchhas suggested that NSAIDs may be effective in preventing colorectalcancer. Sulindac reduces the growth of colon polyps in patientswith familial adenomatous polyposis (FAP). Since most colon cancersdevelop from colon polyps, stopping polyp growth may reduce cancerrisk.

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

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

"In looking for a better colon cancer preventive drug, wedecided to study derivatives of sulindac, to find the active ingredientresponsible for reducing colon polyps. The object was to finda better way to deliver the active ingredient and reduce the sideeffects."

Several research papers suggested that sulindac's side effectswere related to the production of prostaglandins. Sulindac inhibitsproduction of prostaglandins, and many researchers believe thatstopping prostaglandin production prevents tumor formation, accordingto Dr. Alberts.

However, more recent studies conflict with this viewpoint andshow 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 sulindacsulfone was not shown to be active as an anti-inflammatory agent,and it does not inhibit prostaglandin production.

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

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