Randomized, placebo-controlled, esophageal squamous cell cancer chemoprevention trial of selenomethionine and celecoxib

Paul John Limburg, Wenqiang Wei, Dennis J. Ahnen, Youlin Qiao, Ernest T. Hawk, Guoqing Wang, Carol A. Giffen, Guiqi Wang, Mark J. Roth, Ning Lu, Edward L. Korn, Yurong Ma, Kathleen L. Caldwell, Zheiwei Dong, Philip R. Taylor, Sanford M. Dawsey

Research output: Contribution to journalArticle

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Abstract

Background & Aims: Esophageal squamous cell carcinoma remains a leading cause of cancer death worldwide. Squamous dysplasia, the accepted histological precursor for esophageal squamous cell carcinoma, represents a potentially modifiable intermediate end point for chemoprevention trials in high-risk populations. Methods: We conducted a randomized, controlled trial of selenomethionine 200 μg daily and/or celecoxib 200 mg twice daily (2 × 2 factorial design) among residents of Linxian, People's Republic of China. Subjects had histologically confirmed mild or moderate esophageal squamous dysplasia at baseline. Esophagogastroduodenoscopy was performed before and after a 10-month intervention. Per-subject change (regression, stable, or progression) in the worst dysplasia grade was defined as the primary end point. Results were compared by agent group (selenomethionine vs placebo; celecoxib vs placebo). Results: Two hundred sixty-seven subjects fulfilled all eligibility criteria, and 238 (89%) completed the trial. Overall, selenomethionine resulted in a trend toward increased dysplasia regression (43% vs 32%) and decreased dysplasia progression (14% vs 19%) compared with no selenomethionine (P = .08). In unplanned stratified analyses, selenomethionine favorably affected a change in dysplasia grade among 115 subjects with mild esophageal squamous dysplasia at baseline (P = .02), but not among 123 subjects with moderate esophageal squamous dysplasia at baseline (P = 1.00). Celecoxib status did not influence changes in dysplasia grade overall (P = .78) or by baseline histology subgroup. Conclusions: After a 10-month intervention, neither selenomethionine nor celecoxib inhibited esophageal squamous carcinogenesis for all high-risk subjects. However, among subjects with mild esophageal squamous dysplasia at baseline, selenomethionine did have a protective effect. Although it is based on unplanned stratified analyses, this finding is the first report of a possible beneficial effect for any candidate esophageal squamous cell carcinoma chemopreventive agent in a randomized controlled trial.

Original languageEnglish (US)
Pages (from-to)863-873
Number of pages11
JournalGastroenterology
Volume129
Issue number3
DOIs
StatePublished - Sep 2005

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Celecoxib
Selenomethionine
Squamous Cell Neoplasms
Chemoprevention
Esophageal Neoplasms
Placebos
Randomized Controlled Trials
Digestive System Endoscopy
Cause of Death
China
Histology
Carcinogenesis

ASJC Scopus subject areas

  • Gastroenterology

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Randomized, placebo-controlled, esophageal squamous cell cancer chemoprevention trial of selenomethionine and celecoxib. / Limburg, Paul John; Wei, Wenqiang; Ahnen, Dennis J.; Qiao, Youlin; Hawk, Ernest T.; Wang, Guoqing; Giffen, Carol A.; Wang, Guiqi; Roth, Mark J.; Lu, Ning; Korn, Edward L.; Ma, Yurong; Caldwell, Kathleen L.; Dong, Zheiwei; Taylor, Philip R.; Dawsey, Sanford M.

In: Gastroenterology, Vol. 129, No. 3, 09.2005, p. 863-873.

Research output: Contribution to journalArticle

Limburg, PJ, Wei, W, Ahnen, DJ, Qiao, Y, Hawk, ET, Wang, G, Giffen, CA, Wang, G, Roth, MJ, Lu, N, Korn, EL, Ma, Y, Caldwell, KL, Dong, Z, Taylor, PR & Dawsey, SM 2005, 'Randomized, placebo-controlled, esophageal squamous cell cancer chemoprevention trial of selenomethionine and celecoxib', Gastroenterology, vol. 129, no. 3, pp. 863-873. https://doi.org/10.1053/j.gastro.2005.06.024
Limburg, Paul John ; Wei, Wenqiang ; Ahnen, Dennis J. ; Qiao, Youlin ; Hawk, Ernest T. ; Wang, Guoqing ; Giffen, Carol A. ; Wang, Guiqi ; Roth, Mark J. ; Lu, Ning ; Korn, Edward L. ; Ma, Yurong ; Caldwell, Kathleen L. ; Dong, Zheiwei ; Taylor, Philip R. ; Dawsey, Sanford M. / Randomized, placebo-controlled, esophageal squamous cell cancer chemoprevention trial of selenomethionine and celecoxib. In: Gastroenterology. 2005 ; Vol. 129, No. 3. pp. 863-873.
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T1 - Randomized, placebo-controlled, esophageal squamous cell cancer chemoprevention trial of selenomethionine and celecoxib

AU - Limburg, Paul John

AU - Wei, Wenqiang

AU - Ahnen, Dennis J.

AU - Qiao, Youlin

AU - Hawk, Ernest T.

AU - Wang, Guoqing

AU - Giffen, Carol A.

AU - Wang, Guiqi

AU - Roth, Mark J.

AU - Lu, Ning

AU - Korn, Edward L.

AU - Ma, Yurong

AU - Caldwell, Kathleen L.

AU - Dong, Zheiwei

AU - Taylor, Philip R.

AU - Dawsey, Sanford M.

PY - 2005/9

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N2 - Background & Aims: Esophageal squamous cell carcinoma remains a leading cause of cancer death worldwide. Squamous dysplasia, the accepted histological precursor for esophageal squamous cell carcinoma, represents a potentially modifiable intermediate end point for chemoprevention trials in high-risk populations. Methods: We conducted a randomized, controlled trial of selenomethionine 200 μg daily and/or celecoxib 200 mg twice daily (2 × 2 factorial design) among residents of Linxian, People's Republic of China. Subjects had histologically confirmed mild or moderate esophageal squamous dysplasia at baseline. Esophagogastroduodenoscopy was performed before and after a 10-month intervention. Per-subject change (regression, stable, or progression) in the worst dysplasia grade was defined as the primary end point. Results were compared by agent group (selenomethionine vs placebo; celecoxib vs placebo). Results: Two hundred sixty-seven subjects fulfilled all eligibility criteria, and 238 (89%) completed the trial. Overall, selenomethionine resulted in a trend toward increased dysplasia regression (43% vs 32%) and decreased dysplasia progression (14% vs 19%) compared with no selenomethionine (P = .08). In unplanned stratified analyses, selenomethionine favorably affected a change in dysplasia grade among 115 subjects with mild esophageal squamous dysplasia at baseline (P = .02), but not among 123 subjects with moderate esophageal squamous dysplasia at baseline (P = 1.00). Celecoxib status did not influence changes in dysplasia grade overall (P = .78) or by baseline histology subgroup. Conclusions: After a 10-month intervention, neither selenomethionine nor celecoxib inhibited esophageal squamous carcinogenesis for all high-risk subjects. However, among subjects with mild esophageal squamous dysplasia at baseline, selenomethionine did have a protective effect. Although it is based on unplanned stratified analyses, this finding is the first report of a possible beneficial effect for any candidate esophageal squamous cell carcinoma chemopreventive agent in a randomized controlled trial.

AB - Background & Aims: Esophageal squamous cell carcinoma remains a leading cause of cancer death worldwide. Squamous dysplasia, the accepted histological precursor for esophageal squamous cell carcinoma, represents a potentially modifiable intermediate end point for chemoprevention trials in high-risk populations. Methods: We conducted a randomized, controlled trial of selenomethionine 200 μg daily and/or celecoxib 200 mg twice daily (2 × 2 factorial design) among residents of Linxian, People's Republic of China. Subjects had histologically confirmed mild or moderate esophageal squamous dysplasia at baseline. Esophagogastroduodenoscopy was performed before and after a 10-month intervention. Per-subject change (regression, stable, or progression) in the worst dysplasia grade was defined as the primary end point. Results were compared by agent group (selenomethionine vs placebo; celecoxib vs placebo). Results: Two hundred sixty-seven subjects fulfilled all eligibility criteria, and 238 (89%) completed the trial. Overall, selenomethionine resulted in a trend toward increased dysplasia regression (43% vs 32%) and decreased dysplasia progression (14% vs 19%) compared with no selenomethionine (P = .08). In unplanned stratified analyses, selenomethionine favorably affected a change in dysplasia grade among 115 subjects with mild esophageal squamous dysplasia at baseline (P = .02), but not among 123 subjects with moderate esophageal squamous dysplasia at baseline (P = 1.00). Celecoxib status did not influence changes in dysplasia grade overall (P = .78) or by baseline histology subgroup. Conclusions: After a 10-month intervention, neither selenomethionine nor celecoxib inhibited esophageal squamous carcinogenesis for all high-risk subjects. However, among subjects with mild esophageal squamous dysplasia at baseline, selenomethionine did have a protective effect. Although it is based on unplanned stratified analyses, this finding is the first report of a possible beneficial effect for any candidate esophageal squamous cell carcinoma chemopreventive agent in a randomized controlled trial.

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