BackgroundChemoradiotherapy complications has always been of great concern to both clinicians and patients during the course of treatment. The purpose of the present study was to examine the effectiveness of oral famotidine on the reduction of hematologic complications of patients with esophageal and gastric cardia cancers undergoing radiotherapy.MethodsA single-blind controlled trial was conducted on 60 patients with esophageal and cardia cancers, who were undergoing chemoradiotherapy. Patients were randomly assigned to 2 groups with 30 patients to receive either 40 mg of oral famotidine (daily and 4 h before each session) or placebo. Complete blood count with differential, platelet counts, and hemoglobin levels were obtained weekly during treatment. The main outcome variables were lymphocytopenia, granulocytopenia, thrombocytopenia, and anemia.ResultsThe findings indicated a significant effect of famotidine on reduction of thrombocytopenia among intervention group compared to control group (P< 0.0001). Even so, the effect of intervention was not significant for other outcome variables (All,P≥ 0.05). The lymphocyte (P= 0.007) and platelet (P= 0.004) counts were also significantly greater in famotidine group in comparison with placebo group at the end of the study.ConclusionAs evidenced by the findings of the current study, famotidine might be recommended as an effective radioprotective agent among patients with esophageal and gastric cardia cancers to prevent Leukocyte and platelet reduction to some extent.Trial registrationThis study was prospectively registered at irct.ir (Iranian Registry of Clinical Trials) with the code IRCT20170728035349N1, 2020-08-19.