A Study Comparing the Effects of Targeted Intra-Arterial and Systemic Chemotherapy in an Orthotopic Mouse Model of Pancreatic Cancer

Abstract

Abstract Systemic chemotherapy is the first line treatment for patients with unresectable pancreatic cancer, however, insufficient drug delivery to the pancreas is a major problem resulting in poor outcomes. We evaluated the therapeutic effects of targeted intra-arterial (IA) delivery of gemcitabine directly into the pancreas in an orthotopic mouse model of pancreatic cancer. Nude mice with orthotopic pancreatic tumors were randomly assigned into 3 groups receiving gemcitabine: systemic intravenous (IV) injection (low: 0.3 mg/kg and high: 100 mg/kg) and direct IA injection (0.3 mg/kg). Treatments were administered weekly for 2 weeks. IA treatment resulted in a significantly greater reduction in tumor growth compared to low IV treatment. To achieve a comparable reduction in tumor growth as seen with IA treatment, gemcitabine had to be given IV at over 300x the dose (high IV treatment) which was associated with some toxicity. After 2 weeks, tumor samples from animals treated with IA gemcitabine had significantly lower residual cancer cells, higher cellular necrosis and evidence of increased apoptosis when compared to animals treated with low IV gemcitabine. Our study shows targeted IA injection of gemcitabine directly into the pancreas, via its arterial blood supply, has a superior therapeutic effect in reducing tumor growth compared to the same concentration administered by conventional systemic injection.