OBJECTIVE We evaluated efficacy and safety of XELOX in previously untreated patients with AGC. METHODS Patients received intravenous oxaliplatin 130 mg/m(2) over 2 h on day 1 plus oral capecitabine 1,000 mg/m(2) twice daily on days 1-14, every 3 weeks (XELOX). Treatment was continued until disease progression, intolerable toxicities or eight cycles reached. All tumour evaluations were reviewed and confirmed centrally. Design was according to Ensign's three-stage method. RESULTS Fifty-four patients (37 men) were enrolled; median age 57 years (range 29-70). In total, 311 cycles of XELOX were delivered. Overall response rate was 63% (95% CI, 50-76%), with 3 complete and 31 partial responses. At 13 months' median follow-up, median progression-free and overall survival were 5.8 (95% CI, 4.4-7.2) and 11.9 months (95% CI, 8.8-15.1), respectively. The most common haematological adverse event was anaemia (70% of patients). Grade 3-4 neutropenia was observed in four patients, with neutropenic fever in only one patient. Most common non-haematological toxicities were neuropathy (70%), vomiting (50%), diarrhoea (33%), and hand-foot syndrome (HFS) (39%). Grade 3-4 toxicities were rare. Treatment was delayed or the dose reduced in 30 and 15% of cycles, respectively. There was one treatment-related death associated with grade 4 neutropenic sepsis. CONCLUSIONS XELOX was active and well tolerated as a first-line therapy for AGC.