Randomized, placebo-controlled, esophageal squamous cell cancer chemoprevention trial of selenomethionine and celecoxib.
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.
Limburg
Paul J
PJ
Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA. limburg.paul@mayo.edu
Wei
Wenqiang
W
Ahnen
Dennis J
DJ
Qiao
Youlin
Y
Hawk
Ernest T
ET
Wang
Guoqing
G
Giffen
Carol A
CA
Wang
Guiqi
G
Roth
Mark J
MJ
Lu
Ning
N
Korn
Edward L
EL
Ma
Yurong
Y
Caldwell
Kathleen L
KL
Dong
Zheiwei
Z
Taylor
Philip R
PR
Dawsey
Sanford M
SM
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*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D010919:Placebos; D011720:Pyrazoles; D013449:Sulfonamides; D012645:Selenomethionine; D000068579:Celecoxib