Abstract 5610: Electric-field assisted delivery of gemcitabine for the treatment of pancreatic cancer.

Abstract

Abstract Pancreatic cancer is the fourth leading cause of cancer death in the world, with an incidence rate approximately equivalent to the death rate. The very poor prognosis for pancreatic cancer can be attributed to late diagnosis and the ineffectiveness of drug delivery to the primary tumor. Poor tissue perfusion plays a substantial role in preventing adequate drug exposure to primary pancreatic tumors. The systemic administration of gemcitabine, the current standard-of-care chemotherapy for pancreatic cancer, has shown limited efficacy for the treatment of pancreatic cancer, with only 5 to 10% of patients demonstrating an objective radiographic response at the primary tumor site. Furthermore, the toxicity associated with systemic chemotherapy has been found to reduce the quality of life of the patient and in extreme cases can be fatal. In an attempt to address the lack of effectiveness of systemically administered chemotherapy and associated toxicity, we have developed modalities for the localized delivery of chemotherapies to pancreatic tumors. These devices rely upon an applied electric potential difference between electrodes to drive chemotherapy into the tumor. This use of an electric potential for local delivery of chemotherapies offers the capability of overcoming considerable flow and pressure gradients. Significant work using an applied electric potential difference for drug transport has been performed in transdermal drug delivery. In the area of oncology, electric field-assisted delivery techniques have been proposed for skin and ocular cancers and have been clinically translated to the treatment of bladder cancers in the electromotive delivery of mitomycin C. This technique, combined with novel device approaches, is particularly well suited for the local treatment of the primary pancreatic tumor. Herein, we report the development of electric field-assisted delivery devices and the testing of these devices in a patient-derived orthotopic xenograft mouse model of pancreatic adenocarcinoma and a healthy canine animal model. The results show that our devices provide a significant increase in the local delivery of gemcitabine while limiting systemic toxicity. Citation Format: James Byrne, Adrian O'Neill, Raheel Jajja, Mary Napier, James C. Luft, William Zamboni, Jen Jen Yeh, Joseph DeSimone. Electric-field assisted delivery of gemcitabine for the treatment of pancreatic cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5610. doi:10.1158/1538-7445.AM2013-5610