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Background-The efficacy and benefit of second-line chemotherapy in advanced pancreatic adenocarcinoma has never been demonstrated although it is regularly used.Patients and methods-A randomized phase II study evaluating oxaliplatin alone(OXA) ,infusional 5-fluorouracil alone(5-FU) and an oxaliplatin/infusional 5-FU combination(OXFU) in untreated advanced pancreatic adenocarcinoma has been conducted.In this trial,a second-line treatment with the OXFU regimen(OXA 130 mg/m2 2-h intravenous(i.v.) infusion combined with 5-FU(1000 mg/m2/day,continuous i.v.,days 1-4) ,every 3 weeks) was offered to patients progressing after single agent treatment.Results-Eighteen out of 32 patients(12 males,median age 57 years) treated in the single agent arms received the OXFU combination in second-line treatment.WHO performance status was at least 2 in 61% of the patients.There was no objective response and 3 patients(17%) had a disease stabilisation.Median time to progression from the start of second-line treatment was 0.9 months.Median overall survival was 4.9 months from the start of front-line therapy and 1.3 months from the start of second-line therapy.Conclusion-The results of this trial bring arguments to support a modest value of second-line chemotherapy for advanced pancreatic adenocarcinoma.