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 du odenum. This study was planned to evaluate the efficacy of omeprazole or ra nitidine 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 t o be treated with cyclophosphamide, methotrexate, and fluorouracil (90 brea st 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 che motherapy (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 hear tburn was assessed weekly. Results: A significant difference was found among the three groups (P = .00 32), as well as between pre- and postCT endoscopic findings (P = .00001). E ndoscopic scores after CT were significantly higher than pretreatment score s 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 pla cebo (P = .0001 and P = .0315, respectively). Epigastric pain and/or heartb urn 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 gast roduodenal injury. Ranitidine is effective in reducing the frequency of ulc ers and upper gastrointestinal symptoms but is not effective in preventing the global endoscopic worsening caused by chemotherapy. The different effic acy of omeprazole and ranitidine can be explained by their different pharma codynamics. J Clin Oncol 18:463-467 (C) 2000 by American Society of Clinica l Oncology.