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. (C) 1996 American Cancer Society.