Authors |
Bertagnolli MM, Eagle CJ, Zauber AG, Redston M, Solomon SD, Kim K, Tang J, Rosenstein RB, Wittes J, Corle D, Hess TM, Woloj GM, Boisserie F, Anderson WF, Viner JL, Bagheri D, Burn J, Chung DC, Dewar T, Foley TR, Hoffman N, Macrae F, Pruitt RE, Saltzman JR, Salzberg B, Sylwestrowicz T, Gordon GB, Hawk ET; APC Study Investigators. |
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Title |
Celecoxib for the prevention of sporadic colorectal adenomas |
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Full source | N Engl J Med 2006;355:873-84 | |
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Abstract |
BACKGROUND:
Studies showing that drugs that inhibit cyclooxygenase-2 (COX-2) reduce
the number of colorectal adenomas in animals and patients with familial
adenomatous polyposis suggest that COX-2 inhibitors may also prevent sporadic
colorectal neoplasia. METHODS: We randomly assigned patients who had adenomas
removed before study entry to receive placebo (679 patients) or 200 mg
(685 patients) or 400 mg (671 patients) of celecoxib twice daily. Randomization
was stratified for the use of low-dose aspirin. Follow-up colonoscopies
were performed at one and three years after randomization. The occurrence
of newly detected colorectal adenomas was compared among the groups with
the life-table extension of the Mantel-Haenszel test. RESULTS: Follow-up
colonoscopies were completed at year 1 in 89.5 percent of randomized patients,
and at year 3 in 75.7 percent. The estimated cumulative incidence of the
detection of one or more adenomas by year 3 was 60.7 percent for patients
receiving placebo, as compared with 43.2 percent for those receiving 200
mg of celecoxib twice a day (risk ratio, 0.67; 95 percent confidence interval,
0.59 to 0.77; P<0.001) and 37.5 percent for those receiving 400 mg
of celecoxib twice a day (risk ratio, 0.55; 95 percent confidence interval,
0.48 to 0.64; P<0.001). Serious adverse events occurred in 18.8 percent
of patients in the placebo group, as compared with 20.4 percent of those
in the low-dose celecoxib group (risk ratio, 1.1; 95 percent confidence
interval, 0.9 to 1.3; P=0.5) and 23.0 percent of those in the high-dose
group (risk ratio, 1.2; 95 percent confidence interval, 1.0 to 1.5; P=0.06).
As compared with placebo, celecoxib was associated with an increased risk
of cardiovascular events (risk ratio for the low dose, 2.6; 95 percent
confidence interval, 1.1 to 6.1; and risk ratio for the high dose, 3.4;
95 percent confidence interval, 1.5 to 7.9). CONCLUSIONS: These findings
indicate that celecoxib is an effective agent for the prevention of colorectal
adenomas but, because of potential cardiovascular events, cannot be routinely
recommended for this indication. (ClinicalTrials.gov number, NCT00005094
[ClinicalTrials.gov].).
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