Effects of Cyclooxygenase-2 Inhibitors on Gastrointestinal Malignancies: a Systematic Review and Meta-analysis.

Aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs) are associated with a reduced risk of gastrointestinal malignancies, which is thought to be mediated mainly through the inhibition of cyclooxygenases-2 (COX-2). Due to the severe side effects of aspirin/NSAIDs, selective COX-2 inhibitors may be a more ideal choice. The objective is to evaluate the association of selective COX-2 inhibitors with gastrointestinal (GI) malignancies and premalignant lesions. We searched for published manuscripts evaluating the association between COX-2 inhibitors and GI malignancies or precancerous lesion. Two investigators independently abstracted the data; then, we conducted the analysis by Review Manager V.5.0; evaluation of effectiveness was performed by an intention to treat (ITT) method. Selective COX-2 inhibitors had no beneficial effects on the progression or regression of esophageal and gastric dysplasia (OR = 1.06, 95% CI 0.63-1.78,  = 0.83 for regression of esophageal dysplasia; OR = 1.06, 95% CI 0.58-1.91,  = 0.86 for progression of esophageal dysplasia; OR = 1.95, 95%CI 0.92-4.17,  = 0.08 for regression of gastric dysplasia; and OR = 0.99, 95%CI 0.68-1.43,  = 0.94 for progression of gastric dysplasia). There is no protective effect on colorectal cancer (OR = 0.89, 95% CI 0.77-1.03,  = 0.11), and the use could not improve the effect of chemoradiation (OR = 1.20, 95% CI 0.46-3.19,  = 0.71). This pooled analysis indicates no meaningful association between selective COX-2 inhibitors and GI malignancies.