Gemcitabine, Oxaliplatin and Capecitabine in Patients With Advanced Cholangiocarcinoma

In Denmark approximately 200 new cases of cholangiocarcinoma are diagnosed every year. No standard treatment exists for patients with advanced cholangiocarcinoma, and improved systemic treatments are needed. Duplets of gemcitabine, oxaliplatin and capecitabine have been evaluated in various cancers and several different regimens are well tolerated and active, especially in upper gastrointestinal cancers, exocrine pancreatic cancer and non-small cell lung cancer. The triplet combination of these agents has not been studied, but a triplet combination of gemcitabine, oxaliplatin and 5-FU infusion has been evaluated in a phase I study. Bi-weekly combination of gemcitabine and oxaliplatin has proven active and tolerable and warrants further study. In addition, fixed dose rate infusion of gemcitabine has shown interesting as the ability of mononuclear cells to accumulate gemcitabine triphosphate during therapy seems to be saturable. We propose a phase I-II study of a bi-weekly schedule of gemcitabine, oxaliplatin and capecitabine. This regimen could be feasible in an out-patients setting. The phase I part is a standard dose escalation study for patients with solid tumors. In the phase II part the recommended dose is studied in patients with advanced cholangiocarcinoma.