Celecoxib for the prevention of colorectal adenomas: Results of a suspended randomized controlled trial

Patricia A. Thompson, Erin L. Ashbeck, Denise Roe, Liane Fales, Julie Buckmeier, Fang Wang, Achyut K Bhattacharyya, Chiu-Hsieh Hsu, Hsiao-Hui Chow, Dennis J. Ahnen, C. Richard Boland, Russell I. Heigh, David E. Fay, Stanley R. Hamilton, Elizabeth T Jacobs, Elena Maria Martinez, David S Alberts, Michael P Lance

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Article numberdjw151
JournalJournal of the National Cancer Institute
Volume108
Issue number12
DOIs
StatePublished - Dec 1 2016

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Celecoxib
Adenoma
Randomized Controlled Trials
Placebos
Selenium
Confidence Intervals
Recurrence
Cyclooxygenase 1
Cyclooxygenase 2 Inhibitors

ASJC Scopus subject areas

  • Medicine(all)
  • Oncology
  • Cancer Research

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Celecoxib for the prevention of colorectal adenomas : Results of a suspended randomized controlled trial. / Thompson, Patricia A.; Ashbeck, Erin L.; Roe, Denise; Fales, Liane; Buckmeier, Julie; Wang, Fang; Bhattacharyya, Achyut K; Hsu, Chiu-Hsieh; Chow, Hsiao-Hui; 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, Michael P.

In: Journal of the National Cancer Institute, Vol. 108, No. 12, djw151, 01.12.2016.

Research output: Contribution to journalArticle

Thompson, Patricia A. ; Ashbeck, Erin L. ; Roe, Denise ; Fales, Liane ; Buckmeier, Julie ; Wang, Fang ; Bhattacharyya, Achyut K ; Hsu, Chiu-Hsieh ; Chow, Hsiao-Hui ; 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, Michael P. / Celecoxib for the prevention of colorectal adenomas : Results of a suspended randomized controlled trial. In: Journal of the National Cancer Institute. 2016 ; Vol. 108, No. 12.
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abstract = "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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T2 - Results of a suspended randomized controlled trial

AU - Thompson, Patricia A.

AU - Ashbeck, Erin L.

AU - Roe, Denise

AU - Fales, Liane

AU - Buckmeier, Julie

AU - Wang, Fang

AU - Bhattacharyya, Achyut K

AU - Hsu, Chiu-Hsieh

AU - Chow, Hsiao-Hui

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, Michael P

PY - 2016/12/1

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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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