TY - JOUR
T1 - Celecoxib for the prevention of colorectal adenomas
T2 - Results of a suspended randomized controlled trial
AU - Thompson, Patricia A.
AU - Ashbeck, Erin L.
AU - Roe, Denise J.
AU - Fales, Liane
AU - Buckmeier, Julie
AU - Wang, Fang
AU - Bhattacharyya, Achyut
AU - Hsu, Chiu Hsieh
AU - Chow, Sherry H.H.
AU - Ahnen, Dennis J.
AU - Boland, C. Richard
AU - Heigh, Russell I.
AU - Fay, David E.
AU - Hamilton, Stanley R.
AU - Jacobs, Elizabeth T.
AU - Martinez, Elena Maria
AU - Alberts, David S.
AU - Lance, Peter
N1 - Publisher Copyright:
© The Author 2016. Published by Oxford University Press. All rights reserved.
PY - 2016/12/1
Y1 - 2016/12/1
N2 - Background: Cyclooxygenase (COX)-2 inhibitors such as celecoxib were designed to preserve anti-inflammatory activity without inhibiting COX-1. Downregulation of COX-2 inhibits colorectal carcinogenesis. Methods: The Selenium and Celecoxib Trial was a randomized, placebo-controlled trial of once-daily selenium 200 mg and celecoxib 400 mg, alone or together, for colorectal adenoma prevention. Men and women between age 40 and 80 years were eligible following colonoscopic removal of adenomas. The primary outcome was development of new adenomas. Celecoxib was suspended early because of cardiovascular toxicity in other trials. Accrual to selenium or placebo continued. Before suspension, 824 participants were randomly assigned to celecoxib or placebo, of whom 712 (86.4%) were available for analysis. All statistical tests were two-sided. Results: In the placebo and celecoxib arms of 356 participants each, adenoma detection was 47.5% and 49.7% (relative risk [RR] = 1.04, 95% confidence interval [CI] = 0.90 to 1.21, P = .58), respectively, after median periods of 13.6 and 14.2 months on intervention. Among participants colonoscoped within 12 months of discontinuing intervention (n=244), overall adenoma recurrence (RR=0.69, 95% CI=0.48 to 0.98, P = .04) and recurrence with advanced adenomas (RR=0.23, 95% CI=0.07 to 0.80, P = .02) were reduced with celecoxib. Reduction of adenoma recurrence was greatest in participants with previous advanced adenomas. Celecoxib increased risk of hypertension in participants with pre-existing cardiovascular risk factors compared with placebo (hazard ratio = 2.19, 95% CI=1.07 to 4.50, P = .03). Conclusions: Limited-duration celecoxib prevents adenoma recurrence in patients with prior high-risk adenomas, in whom strategies to minimize cardiovascular toxicity might be feasible.
AB - Background: Cyclooxygenase (COX)-2 inhibitors such as celecoxib were designed to preserve anti-inflammatory activity without inhibiting COX-1. Downregulation of COX-2 inhibits colorectal carcinogenesis. Methods: The Selenium and Celecoxib Trial was a randomized, placebo-controlled trial of once-daily selenium 200 mg and celecoxib 400 mg, alone or together, for colorectal adenoma prevention. Men and women between age 40 and 80 years were eligible following colonoscopic removal of adenomas. The primary outcome was development of new adenomas. Celecoxib was suspended early because of cardiovascular toxicity in other trials. Accrual to selenium or placebo continued. Before suspension, 824 participants were randomly assigned to celecoxib or placebo, of whom 712 (86.4%) were available for analysis. All statistical tests were two-sided. Results: In the placebo and celecoxib arms of 356 participants each, adenoma detection was 47.5% and 49.7% (relative risk [RR] = 1.04, 95% confidence interval [CI] = 0.90 to 1.21, P = .58), respectively, after median periods of 13.6 and 14.2 months on intervention. Among participants colonoscoped within 12 months of discontinuing intervention (n=244), overall adenoma recurrence (RR=0.69, 95% CI=0.48 to 0.98, P = .04) and recurrence with advanced adenomas (RR=0.23, 95% CI=0.07 to 0.80, P = .02) were reduced with celecoxib. Reduction of adenoma recurrence was greatest in participants with previous advanced adenomas. Celecoxib increased risk of hypertension in participants with pre-existing cardiovascular risk factors compared with placebo (hazard ratio = 2.19, 95% CI=1.07 to 4.50, P = .03). Conclusions: Limited-duration celecoxib prevents adenoma recurrence in patients with prior high-risk adenomas, in whom strategies to minimize cardiovascular toxicity might be feasible.
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U2 - 10.1093/jnci/djw151
DO - 10.1093/jnci/djw151
M3 - Article
C2 - 27530656
AN - SCOPUS:85016022217
SN - 0027-8874
VL - 108
JO - Journal of the National Cancer Institute
JF - Journal of the National Cancer Institute
IS - 12
M1 - djw151
ER -