Background: Survival for adenocarcinoma of the pancreatic remains unchanged over the last two decades. The majority of patients (85%) are diagnosed with an inoperable tumor. Patterns of failure reveal that pancreatic cancer involves three compartments: the pancreatic bed and regional lymph nodes, the liver and the peritoneal surfaces. Twelve patients with advanced, unresectable pancreatic cancer, Stage II/III, were treated with regional intra-arterial chemotherapy and extracorporeal hemofiltration directed towards the pancreatic tumor-bearing area and the liver., Methods: Five patients had an arterial catheter/port system placed within the celiac axis; the rest had an angiographically placed arterial catheter. All patients had a 16 Fr PFM filtration catheter inserted in the vena cava positioning the tip at the level of the diaphragm and then connected to a hemofiltration unit. Mitomycin C was infused over 25 minutes followed by 5-FU over 10 minutes. The hemofiltration was begun before the drug infusion and continued for 70 minutes. The twelve patients underwent 33 cycles of regional chemotherapy plus hemofiltration., Results: Five patients had a partial response (45.5%), five had stable disease (45.5%), and one had progression (9%). Four patients were re-explored with one patient undergoing a curative resection. The average survival for patients with unresectable pancreatic adenocarcinoma is 13 months. Tumor implantation and progression on the peritoneal surfaces remains the major site of treatment failure., Conclusions: Regional chemotherapy plus hemofiltration with MMC and 5-FU appears to improve the response of Stage II/III inoperable pancreatic cancer and can convert some patients to resectability without significant complications and with no mortality.