The Safety and Efficacy of Celecoxib in Children With Familial Adenomatous Polyposis

Lynch, Patrick M.; Ayers, Gregory D.; Hawk, Ernest T.; Richmond, Ellen; Eagle, Craig; Woloj, Mabel; Church, James M.; Hasson, Hennie; Patterson, Sherri; Half, Elizabeth E.; Burke, Carol A.

doi:10.1038/ajg.2009.758

Cited by 73 publications

(53 citation statements)

References 13 publications

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“…Celecoxib, a specific cyclooxygenase-2 (COX-2) inhibitor, is used clinically to relieve arthritic pain and to treat familial adenomatous polyposis [10]. Unrelated to its effect on COX-2, celecoxib has been found to alter the preferred position of ethynylestradiol and 17β-E2 sulfonation from the 3- to the 17- hydroxy group and to increase total sulfonation in a concentration-dependent manner with SULT2A1 [11, 12].…”

Section: Introductionmentioning

confidence: 99%

Celecoxib influences steroid sulfonation catalyzed by human recombinant sulfotransferase 2A1

Ambadapadi

Wang

Palii

et al. 2015

The Journal of Steroid Biochemistry and Molecular Biology

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Celecoxib has been reported to switch the human SULT2A1-catalyzed sulfonation of 17βestradiol (17β-E2) from the 3- to the 17-position. The effects of celecoxib on the sulfonation of selected steroids catalyzed by human SULT2A1 were assessed through in vitro and in silico studies. Celecoxib inhibited SULT2A1-catalyzed sulfonation of dehydroepiandrosterone (DHEA), androst-5-ene-3β, 17β-diol (AD), testosterone (T) and epitestosterone (Epi-T) in a concentration-dependent manner. Low μM concentrations of celecoxib strikingly enhanced the formation of the 17-sulfates of 6-dehydroestradiol (6D-E2), 17β-dihydroequilenin (17β-Eqn), 17β-dihydroequilin (17β-Eq), and 9-dehydroestradiol (9D-E2) as well as the overall rate of sulfonation. For 6D-E2, 9D-E2 and 17β-Eqn, celecoxib inhibited 3-sulfonation, however 3-sulfonation of 17β-Eq was stimulated at celecoxib concentrations below 40 μM. Ligand docking studies in silico suggest that celecoxib binds in the substrate-binding site of SULT2A1 in a manner that prohibits the usual binding of substrates but facilitates, for appropriately shaped substrates, a binding mode that favors 17-sulfonation.

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Section: Introductionmentioning

confidence: 99%

Celecoxib influences steroid sulfonation catalyzed by human recombinant sulfotransferase 2A1

Ambadapadi

Wang

Palii

et al. 2015

The Journal of Steroid Biochemistry and Molecular Biology

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“…In 2000, the FDA approved celecoxib under subpart H (accelerated approval) as adjunctive treatment for FAP. A subsequent study of children with FAP found that celecoxib at a dosage of 16 mg/kg per day for 3 months was well tolerated and reduced the number of colorectal polyps by 44% (18 ). This finding underscores the power of using familial, high-risk cohorts.…”

Section: Colorectal Cancermentioning

confidence: 70%

Cancer Chemoprevention: Successes and Failures

2013

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BACKGROUND Cancer has traditionally been considered a single disease, but it is now known to be far more complex, with an unfolding etiology. In less than 2 centuries, hundreds—if not thousands—of drugs for the treatment of cancer and for palliative care have been developed and tested, with 143 having achieved approval by the US Food and Drug Administration (MediLexicon International; “Cancer Drugs & Oncology Drugs,” http://www.medilexicon.com/drugs-list/cancer.php). Just 13 agents have been approved, however, for treating precancerous lesions or for reducing risk. CONTENT Nonsteroidal antiinflammatory drugs, vitamins, food constituents and spice components, antidiabetic drugs, ω-3 fatty acids, and fiber are just a few of the many classes of compounds that have been tested for their cancer-preventive potential. We highlight some of the agents that have been scrutinized by way of randomized clinical trials in humans for their cancer prevention potential. We summarize the major definitive cancer chemoprevention studies that (a) were successful in demonstrating efficacy and ultimately received regulatory approval; (b) were not successful in demonstrating efficacy or had unacceptable toxicities, but from which the field has learned important lessons; and (c) showed compelling efficacy against surrogate end points but failed to achieve regulatory approval because of a lack of consensus regarding the relevance of those end points to clinical benefit. SUMMARY Chemopreventive studies have provided new insights into early disease pathogenesis, stimulated new risk assessments and models, fostered important research in end point biomarkers, and led to 13 approved agents. The development of safe and effective chemopreventive agents holds tremendous potential for reducing the burden of cancer.

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“…A longer duration trial is still in progress to further address these issues, as the long-term adverse effects of COX-2 inhibitors among children and younger adults are unknown. 26 …”

Section: Current Status Of Cox-2 Inhibitorsmentioning

confidence: 97%

Cyclo-oxygenase-2 inhibitors for chemoprevention of nonmelanoma skin cancer: Is there a role for these agents?

Liebman

Stein

Polsky

2013

Journal of the American Academy of Dermatology

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The Safety and Efficacy of Celecoxib in Children With Familial Adenomatous Polyposis

Abstract: Celecoxib at a dose of 16 mg/kg/day, corresponding to the adult dose of 400 mg BID, is safe, well tolerated, and significantly reduced the number of colorectal polyps in children with FAP.

Cited by 73 publications

References 13 publications

Celecoxib influences steroid sulfonation catalyzed by human recombinant sulfotransferase 2A1

Celecoxib influences steroid sulfonation catalyzed by human recombinant sulfotransferase 2A1

Cancer Chemoprevention: Successes and Failures

Cyclo-oxygenase-2 inhibitors for chemoprevention of nonmelanoma skin cancer: Is there a role for these agents?

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