Background: Gastric cancer is an important health problem across the world. Chemotherapy in combination with local treatment is the standard treatment for locally advanced gastroesophageal junction (EGJ) cancers. The purpose of this study was to evaluate response and tolerability to neoadjuvant regimen combining epirobicin, oxaliplatin and capecitabin (EOX) in locoregionally advanced gastric cancer.Methods: We recruited 28 patients with histologically confirmed advanced gastric or EGJ adenocarcinoma in this study performed in the Cancer Institute of Imam Khomeini Hospital in Tehran, Iran in 2010-2011. Staging workup included chest and abdominal computed tomography (CT) scans, upper gastrointestinal endoscopy, endoscopic ultrasonography (EUS), measurement of carcinoembryonic antigen (CEA), complete blood cell count (CBC), and liver and renal function tests. After three treatment cycles with EOX regimen, we evaluated response to the neoadjuvant chemotherapy by performing endoscopic ultrasonography (EUS) and chest and abdominal CT scans.Results: The mean age of the patients was 56.64±11.08 years (ranging from 37 to 78 years). Most patients were classified as having stage III (98.8%) cancer before chemotherapy while most were classified as stage II (57.14%) after the treatment. Only 28.5% of tumors were resectable before chemotherapy, but 82.1% of them were resectable upon the treatment. 75% of tumors were downstaged after chemotherapy.Conclusion: Regarding the acceptable response and downstaging of tumors and low toxicity of EOX regimen in locoregionally advanced gastric cancer, evaluation of this regimen as a neoadjuvant chemotherapy in larger phase III clinical trials in Iranian patients would be both necessary and logical.