A combination of esomeprazole and aspirin reduces tissue concentrations of prostaglandin E(2) in patients with Barrett's esophagus.
BACKGROUND& AIMS: Proton pump inhibitors and nonsteroidal anti-inflammatory drugs might prevent esophageal adenocarcinoma in patients with Barrett's esophagus (BE), but there are limited data from clinical trials to support this concept. We conducted a randomized, double-blind, placebo-controlled, phase 2 trial to assess the effects of the combination of aspirin (3 different doses) and esomeprazole on tissue concentrations of prostaglandin (PG) E(2) in patients with BE with no dysplasia or low-grade dysplasia.


METHODS
Participants were recruited through the multicenter Cancer Prevention Network and randomly assigned to groups that were given 40 mg esomeprazole twice daily in combination with an aspirin placebo once daily (arm A; n = 30), with 81 mg aspirin once daily (arm B; n = 47), or with 325 mg aspirin once daily (arm C; n = 45) for 28 days. We collected esophageal biopsy specimens before and after the intervention period to determine the absolute change in mean concentration of PGE(2) (the primary end point).


RESULTS
Based on data from 114 patients, baseline characteristics were similar among groups. The absolute mean tissue concentration of PGE(2) was reduced by 67.6 ± 229.68 pg/mL in arm A, 123.9 ± 284.0 pg/mL in arm B (P = .10 vs arm A), and 174.9 ± 263.62 pg/mL in arm C (P = .02 vs arm A).


CONCLUSIONS
In combination with esomeprazole, short-term administration of higher doses of aspirin, but not lower doses or no aspirin, significantly reduced tissue concentrations of PGE(2) in patients with BE with either no dysplasia or low-grade dysplasia. These data support further evaluation of higher doses of aspirin and esomeprazole to prevent esophageal adenocarcinoma in these patients. Clinical trial registration number NCT00474903.
Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA. gary.falk@uphs.upenn.edu
Gary W
GW
Falk
Navtej S
NS
Buttar
Nathan R
NR
Foster
Katie L Allen
KL
Ziegler
Catherine J
CJ
Demars
Yvonne
Y
Romero
Norman E
NE
Marcon
Thomas
T
Schnell
Douglas A
DA
Corley
Prateek
P
Sharma
Marcia R
MR
Cruz-Correa
Chin
C
Hur
David E
DE
Fleischer
Amitabh
A
Chak
Kenneth R
KR
Devault
David S
DS
Weinberg
Gary
G
Della'Zanna
Ellen
E
Richmond
Thomas C
TC
Smyrk
Sumithra J
SJ
Mandrekar
Paul J
PJ
Limburg
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001241:Aspirin / Q000008:administration & dosage* / Q000627:therapeutic use; D001471:Barrett Esophagus / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D015415:Biomarkers / Q000378:metabolism; D001706:Biopsy; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage* / Q000627:therapeutic use; D015232:Dinoprostone / Q000378:metabolism*; D004311:Double-Blind Method; D015536:Down-Regulation; D004359:Drug Therapy, Combination; D064098:Esomeprazole / Q000627:therapeutic use*; D004945:Esophagoscopy; D004947:Esophagus / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D054328:Proton Pump Inhibitors / Q000627:therapeutic use*
D015415:Biomarkers; D016861:Cyclooxygenase Inhibitors; D054328:Proton Pump Inhibitors; D015232:Dinoprostone; D064098:Esomeprazole; D001241:Aspirin