Parenteral and oral routes have been the traditional methods of administering cytotoxic agents to cancer patients. Unfortunately, the maximum potential effect of these cytotoxic agents has been limited because of systemic toxicity and poor tumor perfusion. In an attempt to improve the efficacy of cytotoxic agents while mitigating their side effects, we have developed modalities for the localized iontophoretic delivery of cytotoxic agents. These iontophoretic devices were designed to be implanted proximal to the tumor with external control of power and drug flow. Three distinct orthotopic mouse models of cancer and a canine model were evaluated for device efficacy and toxicity. Orthotopic patient-derived pancreatic cancer xenografts treated biweekly with gemcitabine via the device for 7 weeks experienced a mean log(2) fold change in tumor volume of -0.8 compared to a mean log2 fold change in tumor volume of 1.1 for intravenous (IV) gemcitabine, 3.0 for IV saline, and 2.6 for device saline groups. The weekly coadministration of systemic cisplatin therapy and transdermal device cisplatin therapy significantly increased tumor growth inhibition and doubled the survival in two aggressive orthotopic models of breast cancer. The addition of radiotherapy to this treatment further extended survival. Device delivery of gemcitabine in dogs resulted in more than 7-fold difference in local drug concentrations and 25-fold lower systemic drug levels than the IV treatment. Overall, these devices have potential paradigm shifting implications for the treatment of pancreatic, breast, and other solid tumors.

L'invention porte sur un systeme de neuromodulation pour traiter des syndromes d'insuffisance cardiaque aigue, lequel systeme de neuromodulation comprend un premier catheter ayant un element de therapie parasympathique concu pour etre positionne a l'interieur d'un premier vaisseau sanguin, tel qu'une veine cave superieure, et un element de therapie sympathique de second catheter concu pour etre positionne a l'interieur d'un second vaisseau sanguin, different, tel que l'artere pulmonaire. Les catheters comprennent un systeme dans lequel l'un des catheters est dispose de maniere coulissante sur l'autre des catheters. Le systeme peut en outre etre dispose de maniere coulissante sur un troisieme element allonge tel qu'un catheter Swan-Ganz pouvant etre positionne a l'interieur d'une artere pulmonaire, de telle sorte que le catheter Swan-Ganz peut etre utilise pour surveiller des parametres, tels que la pression sanguine et le debit cardiaque durant une therapie de neuromodulation. L'element de therapie parasympathique est excite pour administrer une therapie de neuromodulation a une fibre de nerf parasympathique, tel qu'un nerf vague, tandis que l'element de therapie sympathique est excite pour administrer une therapie de neuromodulation a une fibre de nerf sympathique, telle qu'une fibre de nerf cardiaque sympathique. Pour le traitement de syndromes d'insuffisance cardiaque aigue, la therapie de neuromodulation peut etre utilisee pour abaisser la frequence cardiaque et augmenter l'inotropie cardiaque.