A combination of esomeprazole and aspirin reduces tissue concentrations of
prostaglandin E(2) in patients with Barrett's esophagus.
Author(s): Falk GW, Buttar NS, Foster NR, Ziegler KL, Demars CJ, Romero Y, Marcon NE,
Schnell T, Corley DA, Sharma P, Cruz-Correa MR, Hur C, Fleischer DE, Chak A,
Devault KR, Weinberg DS, Della'Zanna G, Richmond E, Smyrk TC, Mandrekar SJ,
Limburg PJ; Cancer Prevention Network.
Affiliation(s): Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania 19104,
USA. gary.falk@uphs.upenn.edu
Publication date & source: 2012, Gastroenterology. , 143(4):917-26
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.
|