Aspirin and PPIs Might Prevent Cancer in Barrett Esophagus

In the largest randomized U.S. trial to date, a combination regimen reduced levels of a biomarker for increased production of the COX-2 enzyme, which is implicated in carcinogenesis.

Preclinical data suggest that nonsteroidal anti-inflammatory drugs (NSAIDs), particularly aspirin, may protect against the development of esophageal adenocarcinoma (EAC) by inhibiting the cyclooxygenase 1 and 2 (COX-1 and COX-2) enzymes, which regulate prostaglandin E2 (PGE2) production. A proposed mechanism for Barrett esophagus (BE) carcinogenesis is induced up-regulation of COX-2 (with high levels of PGE2 production) from acid, bile salt, or both. If this biological premise is correct, treatment with a proton-pump inhibitor (PPI) combined with aspirin might be chemopreventive.

To investigate this possibility, researchers randomized 122 patients with histologically confirmed BE from multiple centers to receive esomeprazole (40 mg twice daily) plus either low-dose aspirin (81 mg daily), high-dose aspirin (325 mg daily), or aspirin placebo for 28 days. Randomization was employed using a 1:1.5:1.5 ratio and stratified by gender, length of BE segment (circumferential involvement <5 cm or 5 cm), and baseline dysplasia status (none, low grade, or indefinite). Before and after treatment, esophageal biopsies were taken to measure PGE2 levels in tissue, with correction for tissue weight.

Of 114 participants evaluated, the low-dose and high-dose aspirin arms showed both absolute decrease (primary endpoint) and percent change decrease (secondary endpoint) in PGE2 concentrations from baseline to postintervention (P0.0004). The placebo arm showed no significant change. Compared with the placebo arm, the high-dose aspirin arm had an absolute decrease in PGE2 values (P=0.02) and a percent change decrease (P<0.0001) in PGE2 values. Low-dose aspirin plus PPI did not result in a significant decrease in PGE2 values.

CITATION(S):

Falk GW et al. A combination of esomeprazole and aspirin reduces tissue concentrations of prostaglandin E2 in patients with Barrett's esophagus. Gastroenterology 2012 Oct; 143:917.