Intratumoral chemotherapy for liver cancer using biodegradable polymer implants

Cancer is the second leading cause of death in the United States, behind only heart disease. Many cancers, particularly solid tumors, are inaccessible to surgery, and current systemic chemotherapy regimens are extremely limited. As a result, developing new treatments for unresectable tumors that minimize side effects is an active area of research. For example, image-guided radiofrequency (RF) ablation has had considerable success for treatment of liver tumors, but tumor recurrence at the periphery of the original tumor site is common. Recent work has proposed improving the efficacy of RF ablation by delivering a drug to the treatment area with a chemotherapeutic, biodegradable implant made of poly(D,L-lactide-co-glycolide) (PLGA). Previous studies have shown that these implants can successfully deliver antineoplastic drugs to normal and ablated liver in animal models. To establish the efficacy of these implants in treating tumors, drug-releasing PLGA implants were manufactured and tested in a rabbit liver tumor model both with and without radiofrequency ablation. Information gathered from the tumor drug distributions was used to develop a computer simulation for comparing alternative tumor treatment configurations. Optimal combined treatments were developed using the simulation and further validated with an animal model. The result of these studies is a comprehensive strategy for treating unresectable tumors with drug-containing implants and RF ablation that may ultimately impact treatment of unresectable tumors in humans.