Researchers from the Netherlands and the USA investigated whether sulindac, a nonsteroidal antiinflammatory drug (NSAID), acts as a chemopreventive agent in patients with familial adenomatous polyposis.
A total of 41 young individuals (age range, 8 to 25 years) were included in the randomized, double blind, placebo-controlled study.
All patients were genotypically affected with familial adenomatous polyposis but phenotypically unaffected.
The subjects received either 75 or 150 mg of sulindac orally, twice a day, or identical-appearing placebo tablets for 48 months.
The number and size of new adenomas and side effects of therapy were evaluated every 4 months, for 4 years.
In addition, the levels of 5 major prostaglandins were serially measured in biopsy specimens of normal-appearing colorectal mucosa.
After 4 years of treatment, the average rate of compliance exceeded 76% in the sulindac group.
The team found that mucosal prostaglandin levels were lower in this group than in the placebo group.
During the course of the study, adenomas developed in 9 of 21 subjects (43%) in the sulindac group and 11 of 20 subjects in the placebo group (55%).
There were found to be no significant differences in the mean number or size of polyps between the groups.
| Prophylactic colectomy remains treatment of choice in familial adenomatous polyposis.
| New England Journal of Medicine |
Furthermore, sulindac was not found to slow the development of adenomas, according to an evaluation involving linear longitudinal methods.
Dr Francis M. Giardiello, of the Johns Hopkins University School of Medicine, Baltimore, Maryland, USA, said on behalf of colleagues, "Standard doses of sulindac did not prevent the development of adenomas in subjects with familial adenomatous polyposis."
"Our results do not provide support for the use of NSAIDs, such as sulindac, for the primary treatment of familial adenomatous polyposis.
"Prophylactic colectomy remains the treatment of choice to prevent colorectal cancer in patients with this disorder," it was concluded.
In an accompanying Editorial, Ian Chau and David Cunningham, of the Royal Marsden Hospital, Surrey, England, point out that determining the optimal dose, schedule, and duration of this treatment for malignant disease, in the appropriate clinical context, is a major challenge.
"With these imperatives in mind, and despite the relatively disappointing results with respect to their ability to prevent adenomatous polyps in patients in familial adenomatous polyposis, NSAIDs and cyclooxygenase-2 inhibitors may yet be shown to have a role in the primary prevention or treatment of established colorectal cancer," they conclude.