title: Randomized, placebo-controlled, esophageal squamous cell cancer chemoprevention trial of selenomethionine and celecoxib.
abstract: OBJECTIVE
  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 microg daily and/or celecoxib 200 mg twice daily (2 x 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.
authors.affiliation: Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA. limburg.paul@mayo.edu
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Limburg
authors.forename: Wenqiang
authors.initials: W
authors.lastname: Wei
authors.forename: Dennis J
authors.initials: DJ
authors.lastname: Ahnen
authors.forename: Youlin
authors.initials: Y
authors.lastname: Qiao
authors.forename: Ernest T
authors.initials: ET
authors.lastname: Hawk
authors.forename: Guoqing
authors.initials: G
authors.lastname: Wang
authors.forename: Carol A
authors.initials: CA
authors.lastname: Giffen
authors.forename: Guiqi
authors.initials: G
authors.lastname: Wang
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Roth
authors.forename: Ning
authors.initials: N
authors.lastname: Lu
authors.forename: Edward L
authors.initials: EL
authors.lastname: Korn
authors.forename: Yurong
authors.initials: Y
authors.lastname: Ma
authors.forename: Kathleen L
authors.initials: KL
authors.lastname: Caldwell
authors.forename: Zheiwei
authors.initials: Z
authors.lastname: Dong
authors.forename: Philip R
authors.initials: PR
authors.lastname: Taylor
authors.forename: Sanford M
authors.initials: SM
authors.lastname: Dawsey
mesh_terms: D000328:Adult; D000368:Aged; D000428:Alcohol Drinking; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D001706:Biopsy; D002294:Carcinoma, Squamous Cell / Q000473:pathology / Q000517:prevention & control*; D000068579:Celecoxib; D004724:Endoscopy; D004938:Esophageal Neoplasms / Q000473:pathology / Q000517:prevention & control*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010919:Placebos; D011720:Pyrazoles / Q000627:therapeutic use*; D012645:Selenomethionine / Q000627:therapeutic use*; D012907:Smoking; D013449:Sulfonamides / Q000627:therapeutic use*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D010919:Placebos; D011720:Pyrazoles; D013449:Sulfonamides; D012645:Selenomethionine; D000068579:Celecoxib