Gemcitabine and oxaliplatin (GEMOX) are active as first-line therapy against advanced pancreatic cancer. This study aims to evaluate the activity and tolerability of this combination in patients refractory to standard gemcitabine (GEM). A total of 33 patients (median age of 57) were included with locally advanced and metastatic evaluable diseases, who had progressed during or following GEM therapy. The GEMOX regimen consisted of 1000 mg m(-2) of GEM at a 100-min infusion on day 1, followed on day 2 by 100 mg m(-2) of oxaliplatin at a 2-h infusion; a cycle that was given every 2 weeks. All patients received at least one cycle of GEMOX (median 5; range 1-29). Response by 31 evaluable patients was as follows: PR: 7/31(22.6%), s.d. > or = 8 weeks: 11/31(35.5%), s.d. < 8 weeks: 1/31(3.2%), PD: 12/31(38.7%). Median duration of response and TTP were 4.5 and 4.2 months, respectively. Median survival was 6 months (range 0.5-21). Clinical benefit response was observed in 17/31 patients (54.8%). Grade III/IV non-neurologic toxicities occurred in 12/33 patients (36.3%), and grade I, II, and III neuropathy in 17(51%), 3(9%), and 4(12%) patients, respectively. GEMOX is a well-tolerated, active regimen that may provide a benefit to patients with advanced pancreatic cancer after progression following standard gemcitabine treatment.