Low-Dose Aspirin Suppresses Mucosal PGE2

SAN DIEGO—In anticipation of a phase II chemoprevention study, researchers at the University of Texas M.D. Anderson Cancer Center determined that low doses of aspirin work as well in suppressing prostaglandin E2 (PGE2) as higher doses. Frank A. Sinicrope, MD, presented the results at an American Gastroenterological Association poster session held during the Digestive Disease Week conference.

Epidemiologic studies indicate that regular aspirin use is associated with a significant reduction in colorectal cancer occurrence and death. “However,” Dr. Sinicrope said, “because of the potential for GI toxicity associated with aspirin, we wanted to see if lower doses would suppress prostaglandin production (believed to be important in the development of colon polyps and cancer) to the same degree as higher doses.”

The researchers recruited 60 patients from an HMO who had a sporadic colorectal adenoma within the past 5 years. They were randomized to one of three daily aspirin doses—81 mg, 325 mg, and 650 mg—or a placebo for 28 days.

To verify compliance, plasma salicylate levels were examined, along with pill counts and patient calendars. Of the 55 evaluable patients, using salicylate levels, Dr. Sinicrope found that 91% of the patients were compliant. Pill counts showed that more than 98% of the aspirin doses were taken by all subjects, and self-reports were concordant with pill counts.

“The 81 mg of aspirin did just as good a job in significantly suppressing PGE2 levels as the higher doses with no toxicity,” he reported. “That means we’ll be using that dose in an upcoming phase II chemoprevention trial. It also means that a high level of compliance can be expected in an at-risk population.”

After the trial, Dr. Sinicrope sent a follow-up questionnaire to the participants. Of the 43 subjects who returned the questionnaire, 19 (44%) said they had continued to take aspirin daily.

“We wanted to figure out the prestudy factors associated with a patient’s decision to continue to take aspirin daily,” he said. “We learned that patients who reported taking vitamins and minerals daily were significantly more likely to take aspirin, as were those who expressed a desire to help future generations at risk.” A post-study query showed that motivators for continued aspirin intake included a desire to lower their own risk of cancer and study participation.