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Sulindac in Managing Familial Adenomatous Polyposis
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Am Fam Physician. 2002 Jul 15;66(2):318-320.
Familial adenomatous polyposis (FAP) is inherited by transmission of a mutation of the APC gene on chromosome 5. The most common manifestations of FAP are multiple colorectal adenomas early in life, with later development of colorectal cancer. Treatment often includes total colectomy, which offers significantly lower morbidity and mortality and a functional outcome; however, cancer of the remaining rectal stump has been reported. Sulindac, a nonsteroidal anti-inflammatory drug, has been found to reduce the size and quantity of rectal adenomatous polyps. Cruz-Correa and associates used a prospective study to examine the long-term use of sulindac in patients with FAP who have had total colectomy with ileorectal anastomosis (IRA).
Twelve patients with FAP who had undergone colectomy with IRA and who had five or more rectal adenomas were included in the study. Subjects who did not have specific contraindications received 150 mg of sulindac twice a day. The number and size of the rectal polyps were assessed at baseline and at follow-ups every four months using flexible sigmoidoscopy. At each examination, biopsy of two adenomas was taken. Sulindac dosing was reduced to 150 mg per day following each sigmoidoscopy that demonstrated a polyp-free rectum. Higher dosing was resumed if the polyps recurred. When more than two polyps were found in the rectum, the two largest were biopsied. Monthly telephone calls were used to monitor for adverse effects, and routine chemistry evaluations were obtained at each four-month visit.
The main end points were the number of polyps and histologic changes with sulindac treatment. Seven of the 12 participants were in the study for a mean of 76.9 months, with six of these patients being essentially polyp-free (fewer than five polyps) on their last visit. Five patients were withdrawn from the study early because of development of rectal cancer, progression of histology, increase in the number of polyps, refractory rectal mucosal erosions, or poor compliance. After the initial 12 months, all patients had a significant regression in polyp number. At final follow-up, there was a significant decrease in the recurrence of higher-grade adenomas. Few adverse effects of sulindac use were noted, although in six of the 12 patients, rectal mucosal erosions were reported at the IRA site.
The authors conclude that both short-term and long-term use of sulindac reduce adenomas in the rectal segments of post-surgical patients with FAP. Higher-grade adenoma recurrence was also significantly decreased. There were no major adverse effects or changes in laboratory chemical tests. Patients receiving sulindac who develop rectal mucosal erosions should reduce the medication dosage. Treatment with sulindac requires regular endoscopic examination to (1) follow polyp response, (2) adjust sulindac dosing appropriately, and (3) identify the occasional cases of rectal cancer.
Cruz-Correa M, et al. Long-term treatment with sulindac in familial adenomatous polyposis: a prospective cohort study. Gastroenterology. March 2002;122:641–5.
Copyright © 2002 by the American Academy of Family Physicians.
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