Secondary Chemoprevention of Barrett's Esophagus With Celecoxib: Results of a Randomized Trial

Barrett’s esophagus is a premalignant condition in which normal squamous epithelium of the esophagus is replaced by specialized columnar mucosa. It occurs as a result of chronic gastroesophageal reflux and is associated with an increased risk of developing esophageal adenocarcinoma. The incidence of esophageal adenocarcinoma in the United States is rapidly increasing (1–4). The 5-year survival rate after surgical resection of esophageal cancer is approximately 24% (5). Although clinical trials evaluating potential new agents and new approaches in the treatment of esophageal adenocarcinoma are underway, this disease remains associated with high morbidity and mortality. Strategies to prevent or reverse esophageal tumorigenesis include antireflux surgery, aggressive medical management of acid secretion, and ablation of premalignant tissue (6–8). With the exception of Barrett’s mucosal ablation with photodynamic therapy for patients with high-grade dysplasia, most strategies have not been effective (9). Photodynamic therapy can ablate high-grade dysplasia and substantially decrease the incidence of adenocarcinoma, but it is expensive and associated with adverse reactions, including prolonged photosensitivity, chest pain, and esophageal stricture (9). Hence, there is an urgent need for newer agents and/or methods to decrease the risk of progression from dysplasia to this deadly cancer. Several epidemiologic studies (10–13) have found that, among patients at risk for esophageal cancer, treatment with aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with a decreased risk of esophageal cancer. One potential mechanism for chemoprevention is inhibition of cyclooxygenase (COX), an enzyme that is crucial to the synthesis of prostaglandins (PGs) from arachidonic acid (14). Esophageal tumorigenesis has been associated with overexpression of the inducible COX isoform COX-2 (15). Treatment with a COX-2 inhibitor led to a reduction in esophageal adenocarcinomas in an animal model of Barrett’s esophagus (16). We report the results of Chemoprevention for Barrett’s Esophagus Trial (CBET), a phase IIb randomized, parallel treatment, placebo-controlled, double-masked multicenter trial evaluating the long-term administration of celecoxib, a selective COX-2 inhibitor, in Barrett’s esophagus patients with lowor high-grade dysplasia.