Randomized trial of omeprazole or ranitidine versus placebo in the prevention of chemotherapy-induced gastroduodenal injury.

PURPOSE: Anticancer drugs may induce acute mucosal injury to stomach and duodenum. This study was planned to evaluate the efficacy of omeprazole or ranitidine in preventing such an injury.

PATIENTS AND

METHODS

Two hundred twenty-eight cancer patients with normal stomach and duodenum or with less than three erosions, who were selected to be treated with cyclophosphamide, methotrexate, and fluorouracil (90 breast carcinoma patients) or fluorouracil alone (138 colon carcinoma patients), were randomly assigned to treatment with omeprazole 20 mg, ranitidine 300 mg, or one placebo tablet a day. Seven days after the second course of chemotherapy (CT), the patients underwent a further esophagogastroduodenoscopy to evaluate the mucosal injury. Endoscopic findings were quantified on the basis of an arbitrary score, and the occurrence of epigastric pain or heartburn was assessed weekly.

RESULTS

A significant difference was found among the three groups (P =.0032), as well as between pre- and postCT endoscopic findings (P =.00001). Endoscopic scores after CT were significantly higher than pretreatment scores in the placebo (P =.003) and ranitidine (P =.003) groups but not in the omeprazole group (P =.354). Acute ulcers were significantly less frequent in patients receiving omeprazole or ranitidine than in those receiving placebo (P =.0001 and P =.0315, respectively). Epigastric pain and/or heartburn were significantly less frequent in patients receiving omeprazole (P =.00124) or ranitidine (P =.038) than in those receiving placebo.

CONCLUSION

Omeprazole is effective in preventing chemotherapy-induced gastroduodenal injury. Ranitidine is effective in reducing the frequency of ulcers and upper gastrointestinal symptoms but is not effective in preventing the global endoscopic worsening caused by chemotherapy. The different efficacy of omeprazole and ranitidine can be explained by their different pharmacodynamics.