LANDMARK ARTICLE - Required reading

 Steinbach G, Lynch PM, Phillips RK, et al.  The effect of celecoxib, a cyclooxygeanse-2 inhibitor, in familial adenomatous polyposis.  N Engl J Med 2000;342:1946-1952.

 Major Findings

 -- Seventy patients with familial adenomatous polyposis syndrome (FAP) were randomly assigned to placebo, celecoxib 100mg bid, or 400 bid.  All had similar number of polyps at baseline.

-- After 6 months, patients on the 400mg bid group had a 28% reduction in number of polyps, and a 30.7% reduction in polyp burden (defined as the sum of all polyp diameters)   as compared with a reduction of 4.5% and 4.9% respectively in the placebo group (p=0.003 for number of polyps, p=0.001 for polyp burden)

-- Among the group receiving 100mg bid, reduction in polyp number and burden were 11.9% and 14.6% respectively (p=0.33)

--  Adverse events were similar in the treated and the placebo group.

 FACTS TO REMEMBER FOR BOARDS

Patients with FAP have a nearly 100% chance of colon cancer.

The genetic defect is a germ-line mutation in the adenomatous polyposis coli (APC) gene

COX-1 is expressed in most tissues, in some of these tissues, COX-1 is beneficial and its inhibition may be detrimental (ie. Gastric mucosal)

COX-2 is induced in response to cytokines and is expressed in inflammatory disease, premalignant lesions and colon cancer

Sulindac, a non-selective COX inhibitor has been shown to be benefical on patients with FAP

Recurrence of adenomas once therapy is discontinued is universal.

Clinical Application

If celecoxib is to be used to reduce the burden of adenomas, the higher dose of 400mg bid must be used.

COX-2 inhibitor therapy should not replace prophylactic colectomy in the management of these patients.

The use of NSAID’s or COX-2 inhibitors is most likely to be of benefit for those patients with FAP who have undergone subtotal colectomy, to reduce the risk of recurrent polyps in the retained rectal tissue.

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