Docetaxel, capecitabine and 5-fluorouracil have been shown to be active in the treatment of metastatic gastric adenocarcinoma. Consistent with this finding, the aim of this study was to test this combination in a clinical trial. Forty-one patients with metastatic gastric adenocarcinoma and a median age of 64 years were recruited for the study. The treatment was based on the administration of docetaxel 60 mg/m2 every 4 weeks, leucovorin 200 mg/m2, 5-fluorouracil 400 mg/m2 bolus, and capecitabine 1000 mg/m2 twice daily on days 1 and 2 every 2 weeks. Patients achieving a clinical benefit were treated, as maintenance immunotherapy, with low-dose interleukin-2 and 13-cis-retinoic acid. The primary end point of this phase II study was the response rate. The secondary end points relied on the evaluation of the immunological parameters, toxicity, and progression-free survival and overall survival. The overall response rate in the 41 evaluable patients was estimated to be 49%. Median progression-free and overall survival was 9.5 and 21.1 months, respectively. Grade 3 and 4 hematological toxicities were neutropenia and thrombocytopenia in 44 and 5% of patients, respectively. A sustained improvement of evaluated immunological parameters with a negligible toxicity profile was observed in the 27 patients treated with interleukin 1-2/13-cis-retinoic acid. Docetaxel in combination with leucovorin, 5-fluorouracil and capecitabine followed by low-dose interleukin 1-2 and 13-cis-retinoic acid is well tolerated, and shows a significant activity in patients with metastatic gastric adenocarcinoma.