OBJECTIVE To determine the activity and the toxicity associated with a low dose regimen of leucovorin (LV) plus 5-fluorouracil (5-FU) combined with oxaliplatin every two weeks (modified FOLFOX 4) as a salvage therapy for advanced gastric cancer patients. METHODS Between December 2003 and December 2004, 33 patients were enrolled in this study. The patients were treated with oxaliplatin 85 mg/m(2) as a 2-hour infusion on the first day plus LV 20 mg/m(2) over 10 minutes. Subsequently, the patients were given a 5-FU bolus 400 mg/m(2) followed by a 22-hour continuous infusion of 600 mg/m(2) on days 1 approximately 2. The treatment was repeated at 2 week intervals. RESULTS The median age of the patients was 50 years (range: 31 approximately 74), 82% (27/33) had the Eastern Cooperative Oncology Group performance status was 0 and 1. Of the 30 patients who could be evaluated for their tumor response, 8 achieved a partial response, with an overall response rate of 26.7% (95% confidence interval (CI): 20.5 approximately 32.7%). Fifteen patients (50%) showed stable disease and 7 patients (23.3%) progressed during the course of treatment. The median time from the start of chemotherapy to progression was 3.5 months (95% CI: 2.6 approximately 4.4 months) and the median overall survival time was 7.9 months (95% CI: 5.9 approximately 9.9 months). The major grade 3/4 hematological toxicity encountered included neutropenia (45.4%) and thrombocytopenia (3.0%). Neutropenic fever occurred during only 2 of the 178 cycles. The most common non-hematological toxicity encountered was grade 1/2 nausea/vomiting, which occurred in 18.2% of patients, diarrhea in 12.1% and neuropathy in 15.2%. There were no treatment related deaths. CONCLUSIONS The modified FOLFOX 4 regimen appears to be a safe and effective salvage therapy for advanced gastric cancer patients.