Chemoprevention With Low-Dose Aspirin Promising In Familial Adenomatous Polyposis

Low-dose aspirin can suppress the recurrence of colorectal polyps larger than 5.0 mm in patients with familial adenomatous polyposis (FAP), according to results of the J-FAPP Study IV.

"Because colorectal polyps larger than 5.0 mm strongly correlate with the development of colorectal cancer, low-dose aspirin could be a useful chemopreventive drug for colorectal cancer prevention in patients with FAP," the authors write in The Lancet Gastroenterology and Hepatology.

Colectomy is currently the only established treatment for preventing colorectal cancer in patients with FAP. The goal of the J-FAPP Study IV was to clarify the individual and joint effects of low-dose aspirin and mesalazine on the recurrence of colorectal polyps in Japanese patients with FAP.

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Eligible patients were 16 to 70 years old, had a history of more than 100 adenomatous polyps in the large intestine, and did not undergo colectomy. Before the study, all colorectal polyps of at least 5.0 mm in diameter were removed. A total of 104 patients were randomly allocated to receive either aspirin (100 mg/day), mesalazine (2 g/day), both aspirin and mesalazine, or neither for eight months.

"In this randomized, double-blind, placebo-controlled, multicenter trial, low-dose aspirin administered for 8 months reduced the incidence of colorectal polyps of more than 5.0 mm in Japanese patients with FAP without a history of colectomy. Mesalazine did not show suppressive effects," report Dr. Hideki Ishikawa of Kyoto Prefectural University of Medicine and colleagues.

At eight months, 26 of 52 of patients (50%) who did not take aspirin had colorectal polyps of at least 5.0 mm, as did 15 of 50 patients (30%) who received any aspirin, 21 of 50 patients (42%) did not receive mesalazine, and 20 of 52 patients (38%) who received any mesalazine.

The adjusted odds ratio for polyp recurrence was 0.37 (95% confidence interval, 0.16 to 0.86) in the patients who received any aspirin and 0.87 (95% CI 0.38 to 2.00) in the patients who received any mesalazine.

"Although further trials are necessary, the use of aspirin in concert with diligent endoscopic removal of adenomas is a promising and well tolerated non-surgical treatment for FAP," the authors conclude.

Dr. Patrick Lynch of the department of gastroenterology, hepatology and nutrition at the University of Texas MD Anderson Cancer Center, in Houston, write in a linked comment, "Having engaged in chemoprevention trials for familial adenomatous polyposis for nearly 30 years, I have come to appreciate the crucial importance of endoscopic endpoints and how they are measured. Although it is unlikely that the emergence of adenomas greater than 5.0 mm in the course of a short trial would meet a U.S. Food and Drug Administration measure of clinical benefit, it does seem likely to be an acceptable endpoint for those who actually care for these patients."

"Many questions remain unanswered by familial adenomatous polyposis chemoprevention trials. The very diversity of agents and settings used in these trials speaks to the lack of consensus on the optimal agent and outcome. It is clear that no agent or combination of agents has yet achieved a substantial result that would imply such a decrease in existing adenomas or prevention of new adenomas as to enable a decrease or cessation of surveillance endoscopy and the elimination (or at least delay) of surgical prophylaxis in a substantial proportion of patients," Dr. Lynch adds.

"In short-term aspirin trials for familial adenomatous polyposis, aspirin provides at most a marginal benefit, as measured by change in adenoma count and size. All trials have probably been underpowered to detect a modest, but potentially significant benefit. But the most vexing challenge has to do with measuring the effect," he points out.

"The measure in the trial by Ishikawa and colleagues - incidence of adenomas larger than 5.0 mm in patients having had such polyps cleared at baseline, as a measure of progression or non-progression over time - is as reasonable as any used to date. Although trial designs will continue to evolve, further efforts to arrive at best practice in trial design and endpoint measures will be essential," Dr. Lynch concludes.

—Reuters Staff

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