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Context Capecitabine has shown efficacy in treatment of metastatic pancreatic cancer. Several researchers have identified thymidine phosphorylase, dihydropyrimidine dehydrogenase, or their ratio as indicators of response to capecitabine in various cancers. Case report We report two patients with metastatic pancreatic carcinoma who had long-term survivals on capecitabine after gemcitabine failure. These two cases prompted us to measure thymidine phosphorylase and dihydropyrimidine dehydrogenase levels to facilitate discourses regarding their relationship with efficacy of capecitabine. We also describe a novel method of measuring thymidine phosphorylase level from serum without an invasive tissue biopsy. One patient is alive as of today, with improved performance status, 50 months after capecitabine was started. CA 19-9 and CT scans remained stable during 57 cycles. Her thymidine phosphorylase level was 1.77 compared to a control level of 1.00. Dihydropyrimidine dehydrogenase level was 4.14 compared to a control level of 1.00. Their ratio was 0.43. The other patient was alive on capecitabine for 24 months. His performance status, bilirubin, AST, and ALT improved on capecitabine. CT scans and CA 19-9 remained stable during this period. He had thymidine phosphorylase level of 5.56, dihydropyrimidine dehydrogenase level of 2.74, and their ratio of 2.03. Conclusion Capecitabine resulted in long term survivals in two patients with metastatic pancreatic cancer after gemcitabine failure. The use of capecitabine as second-line treatment in metastatic pancreatic cancer should be further explored along with the role of thymidine phosphorylase and dihydropyrimidine dehydrogenase levels in its activity. A non-invasive method of thymidine phosphorylase measurement we described should be validated in larger trials.