Background: Preclinical and clinical studies demonstrated that itraconazole, a common anti-fungal agent, has anticancer activity. The purpose of this study was to evaluate the efficacy of the chemotherapy with itraconazole on unresectable, metastatic, and recurrent gastric cancer. Methods: All patients were referred to our clinic with a clinical diagnosis of unresectable gastric cancer. The regimen consisted of 160 mg/m2 nab-paclitaxel IV on day 1, 100 mg/m2 oxaliplatin IV on day 1, 60 mg/m2 S-1 orally on days 1-7, and 400mg itraconazole orally on days -1 to 3, repeated every 3 weeks. Conversion surgery was allowed. The primary endpoint was overall survival (OS). Results: Between 2015 and 2018. 23 patients were enrolled. Their median age was 68 years (range 40-80 years); stomach/gastroesophageal junction: 21/2; Stage IIIA/IIIB/IV: 2/1/20. Among 10 patients who had liver metastases, 2 had simultaneous lung metastases. Nine patients had peritoneal dissemination. Five patients with stage IV had recurrent disease after primary surgery followed by adjuvant S-1. The other 18 patients had no history of surgery or chemotherapy. Response rate was 70% (CR/PR: 2/14). Among 12 patients (67%) who had conversion surgery, R0 resection was conducted in 8 and no residual tumor was observed in 2. Among enrolled 23 patients, median OS was 22 months (95%CI: > 12 months) and 1-year OS rate was 81.8% (95%CI: 46.7%―95.5%). Grade 3/4 neutropenia in 5 (22%), no grade 3/4 thorombocytopenia, grade 2 peripheral sensory neuropathy in 6 (26%). Conclusions: The addition of itraconazole to chemotherapy showed promising efficacy with high conversion surgery rate and with acceptable toxicities. Clinical trial information: UMIN000021340.