Celecoxib for the Prevention of Colorectal Adenomas: Results of a Suspended Randomized Controlled Trial

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. The Selenium and Celecoxib Trial was a randomized, placebo-controlled trial of once-daily selenium 200 µg and...

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Published in:JNCI : Journal of the National Cancer Institute 2016-12, Vol.108 (12)
Main Authors: Thompson, Patricia A, Ashbeck, Erin L, Roe, Denise J, Fales, Liane, Buckmeier, Julie, Wang, Fang, Bhattacharyya, Achyut, Hsu, Chiu-Hsieh, Chow, Sherry H H, Ahnen, Dennis J, Boland, C Richard, Heigh, Russell I, Fay, David E, Hamilton, Stanley R, Jacobs, Elizabeth T, Martinez, Elena Maria, Alberts, David S, Lance, Peter
Format: Article
Language:English
Subjects:
Adenoma - diagnostic imaging
Adenoma - prevention & control
Adenoma - surgery
Aged
Cardiovascular Diseases - chemically induced
Celecoxib - adverse effects
Celecoxib - therapeutic use
Colonoscopy
Colorectal Neoplasms - diagnostic imaging
Colorectal Neoplasms - prevention & control
Colorectal Neoplasms - surgery
Cyclooxygenase 2 Inhibitors - adverse effects
Cyclooxygenase 2 Inhibitors - therapeutic use
Early Termination of Clinical Trials
Female
Follow-Up Studies
Humans
Male
Middle Aged
Neoplasms, Second Primary - diagnostic imaging
Neoplasms, Second Primary - prevention & control
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Summary: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. The Selenium and Celecoxib Trial was a randomized, placebo-controlled trial of once-daily selenium 200 µg 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. 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). Limited-duration celecoxib prevents adenoma recurrence in patients with prior high-risk adenomas, in whom strategies to minimize cardiovascular toxicity might be feasible.
ISSN:0027-8874
1460-2105
DOI:10.1093/jnci/djw151