Medication Summary
NSAIDs have been found to decrease the size of colon polyps in patients with FAP and Gardner syndrome. The first is celecoxib, a COX-2 inhibitor, which was previously approved by the US Food and Drug Administration (FDA) for treatment of colonic polyps in patients with FAP. [19] The indication was rescinded because of incomplete data required by the FDA for the accelerated approval; hence, it is no longer approved for FAP in the United States but is used off-label.
Celecoxib is not curative and has not been shown to reduce the risk of developing adenocarcinoma. A recent trial has also shown celecoxib to show similar efficacy in the pediatric population. [20]
Other NSAIDs used in the past include sulindac and aspirin. Although these medications are effective at reducing the size of colonic polyps, they typically also cause significant GI side effects such as GI bleeding and are not typically used at this time. Sulindac has also been used as an initial conservative treatment for intra-abdominal and abdominal wall desmoids. [21]
Nonsteroidal Anti-inflammatory Agents
Class Summary
These agents inhibit growth of adenomatous polyps and cause regression of existing polyps in patients with familial adenomatous polyposis (FAP).
Celecoxib (Celebrex)
This agent inhibits primarily COX-2. COX-2 has been found to be up-regulated in a variety of premalignant disorders and malignancies. It appears to play role in tumor growth, promotion, and metastasis. NSAIDs have been shown to inhibit angiogenesis in cell culture and rodent models of angiogenesis. Since angiogenesis is a feature of both benign and malignant disease and COX-2 is up-regulated in the neovasculature of malignant tumors and their surrounding stroma, selective COX-2 inhibitors may be able to modify the progression of these disorders through control of angiogenesis.
Growing evidence suggests a protective role for NSAIDs against the development of colorectal cancer. A significant effect in reversing adenoma growth has also been illustrated with the use of celecoxib in patients with FAP. Because of this, the drug is used off-label for FAP. Data are limited for use in children.
Sulindac (Clinoril)
Sulindac is a sulfoxide, which is metabolized to the anti-inflammatory sulfide metabolite and a sulfone metabolite. Both metabolites are known to have apoptotic activity on colonic epithelial cells, but whether this is required for the chemoregressive activity of these drugs is not known. Multiple systemic effects, including analgesia, antipyretic, and anti-inflammatory, are mostly mediated by inhibition of prostaglandin synthesis. This agent may be considered for off-label use in adults with FAP.
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Colon, polyposis syndromes: polyposis coli. Postevacuation image obtained after double-contrast barium enema study shows extensive polyposis of the colon.
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Endoscopic images showing multiple large intestinal polyps in a patient with Gardner syndrome. Courtesy of Christina Surawicz, MD, Harborview Medical Center, Seattle, Wash.
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Surgical specimen of the colon in a patient with familial polyposis after total colectomy with ileoanal anastomosis. Note the carpetlike appearance of the mucosa covered with polyps.
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High-power view of a tubular adenoma. Courtesy of G. Warren, MD, Rose Medical Center, Denver, Colo.
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Villous adenoma showing fingerlike projections stretching from the surface of a polyp downward with minimal branching. Courtesy of D. Owen, MD.
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Plain lateral skull radiograph in a patient with known Gardner syndrome shows a large osteoma in the occipital region (arrows).
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Bland fibrocytic cells of a desmoid tumor growing in a haphazard-to-storiform manner and producing collagen (hematoxylin-eosin, original magnification X100).
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Cyst containing keratinous material (hematoxylin and eosin, original magnification X1.6).
