Pancreatic cancer represents the fifth most common cause of cancer related mortality in the US and is still considered to be incurable. The two chemotherapeutic agents used most commonly are 5-fluorouracil (5-FU) and gemcitabine. Several randomized clinical trials have shown that gemcitabine was slightly better with an overall response rate of 17% and median survival of 5.7 months. Some encouraging results have been observed when gemcitabine is locally administrated to treat patients with unresectable locally advanced pancreatic tumors. However, the improvement in survival rate is limited due to the lack of an appropriate delivery technology. The challenge in treating locally advanced pancreatic cancer remains how to deliver the therapeutic agents directly to the tumors at a high concentration and yet maintain low systemic concentration so that side effects are minimized. FeRx proposes to evaluate the use of magnetically targeted carriers (MTCs) to deliver gemcitabine to pancreatic tumors. MTCs are magnetic microparticles composed of metallic iron and activated carbon capable of binding a wide variety of pharmaceutical agents. MTCs are administered via intra-arterial administration and are localized to the tumors using an externally positioned magnet. FeRx proposes to develop MTC-Gemcitabine to investigate the feasibility to deliver high local concentration of gemcitabine specifically to the pancreas. Preliminary results have indicated that gemcatibine can be used with the MTC technology. In order to prove the usefulness of MTC technology to deliver the drug to pancreas, FeRx proposes: 1) to complete the optimization of the binding and release properties of gemcitabine onto the MTCs and develop the supporting analytical methods, 2) to characterize the in vitro properties of MTC-Gemcitabine, and 3) to evaluate in vivo the effects of MTC-Gemcitabine magnetically delivered to the pancreas of normal swine.
