A Combination of Esomeprazole and Aspirin Reduce Tissue Concentrations of Prostaglandin E2 in Patients with Barrett's Esophagus
Mené sur 114 patients atteints d'un endobrachyœsophage avec ou sans dysplasie de bas grade, cet essai contrôlé multicentrique de phase II évalue les effets d'un traitement combinant l'aspirine et l'ésoméprazole sur les concentrations tissulaires en prostaglandine E2
Proton pump inhibitors (PPIs) 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 II trial to assess the effects of the combination of aspirin (3 different doses) and esomeprazole on tissue concentrations of prostaglandin E2 (PGE2) in patients with BE with no dysplasia or low-grade dysplasia. Participants were recruited through the multi-center Cancer Prevention Network and randomly assigned to groups that were given esomeprazole (40 mg, twice daily) in combination with an aspirin placebo (once daily) (Arm A; n=42), with 81 mg aspirin (once daily) (Arm B; n=63), or with 325 mg aspirin (once daily) (Arm C; n=63) for 28 days. We collected esophageal biopsies before and after the intervention period, to determine the absolute change in mean concentrations of PGE2 (the primary endpoint). Based on data from 114 patients, baseline characteristics were similar among groups. The absolute mean tissue concentrations of PGE2 was reduced by 67.6±229.68 pg/mL in Arm A, was reduced by 123.9±284.0 pg/mL in Arm B (P=.10 vs Arm A), and was reduced by 174.9 ±263.62 pg/mL in Arm C (P=.02 vs Arm A). In combination with esomeprazole, short-term administration of higher doses of aspirin, but not lower doses or no aspirin, significantly reduced tissue concentrations of PGE2 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.
http://linkinghub.elsevier.com/retrieve/pii/S0016508512009523?showall=true