Pancreatic cancer is one of the most intractable of all human cancers. We have previously developed a patient-like model of human pancreatic cancer by surgical orthotopic implantation (SOI). After SOI of the human tumor xenograft PAN-12-JCK into the tail of the nude mouse pancreas, mitomycin C (MMC) and cisplatin (DDP) were administered intraperitoneally at a dose of 4 and 6 mg/kg, respectively, on day-7. The mice were observed for 95 days. There was a statistically significant increase in disease-free and overall survival rates in the MMC- and MMC + DDP-treated groups. Local tumor growth was eliminated only in the group treated with MMC + DDP. Hepatic metastasis and peritoneal disseminations were completely inhibited by MMC but not DDP. This study demonstrates the usefulness of the SOI model of pancreatic cancer to study the differential efficacy of agents affecting primary tumor growth metastasis and survival, thus presenting an opportunity for the discovery of new agents for this highly resistant cancer.