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At the time of diagnosis most of patients present with advanced or metastatic pancreatic cancer, thereby precluding surgicalresection. While the standard of care in the first line setting is established, there are limited data to support a standard second-line chemotherapy regimen. The authors summarize two interesting studies (Abstract #263 and Abstract #287) presented at the 2013 ASCO Gastrointestinal Cancers Symposium. These studies concern two phase II trials about second-line chemotherapy in pancreatic cancer. The first one evaluated the role of fluoropyrimidine as monotherapy versus fluoropyrimidine in combination with irinotecan (Abstract #263) and the second one compared the fluoropyrimidine treatment with the continuation of gemcitabine as monotherapy (Abstract #287).