PURPOSE: There is no effective salvage regimen for failed gemcitabine-based chemotherapy. This study evaluated the efficacy and toxicity of 5-fluorouracil and paclitaxel in patients with gemcitabine-refractory pancreatic cancer. METHODS: Between January 2004 and December 2007, 28 patients with pancreatic cancer previously treated with gemcitabine-based chemotherapy were enrolled. 5-Fluorouracil 1,000 mg/m(2) was infused (days 1, 2, and 3) and paclitaxel 175 mg/m(2) (day 1) was administered every 4 weeks. The primary endpoint of this study was efficacy and toxicity and the secondary endpoint was time to progression and overall survival. RESULTS: A total of 75 cycles were given, for a mean of 2.68 cycles per patient. The response could be evaluated in 20 patients. Two patients (10%) obtained a partial response, and four patients (20%) had stable disease. The median time to progression and overall survival was 2.5 and 7.6 months, respectively. Grade 3/4 hematological toxicity included neutropenia in six patients (21.4%), anemia in one (3.6%), and thrombocytopenia in one (3.6%). One (3.6%) patient experienced grade 4 neuropathy, and two (7.2%) patients experienced grade 3 diarrhea. CONCLUSION: The 5-fluorouracil and paclitaxel combination treatment seems to be effective in patients with advanced pancreatic cancer that did not respond to a gemcitabine-based regimen.