Over 215,000 people will be diagnosed in 2008 with bronchial carcinoma in the U.S. according to the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute. Currently, asthma afflicts 22.9 million people in the U.S., and tracheomalacia is believed to afflict 3 million people in the U.S. In addition to these chronic or deadly conditions, intervention into the bronchial passageways with bronchoscopic procedures can cause bronchial granulation tissue that obstructs airflow. These diseases of the bronchi may potentially be treated with local, direct infusion of medications into the bronchial wall and adventitia (the tissue between smooth muscle layers and cartilage). In fact, data suggests that diseases of the bronchi arise in the sub-epithelial bronchial wall, and thus local treatment beyond the epithelium is warranted. Despite the magnitude of these problems and the potential for a simple solution, there has existed no device useful to deliver safely and reliably into the bronchial wall. Mercator MedSystems has developed a vascular adventitial infusion catheter that has FDA 510(k) clearance to market for use in humans, and now has modified the catheter to target injections into bronchial walls. This is an endoluminal balloon catheter which extrudes a single needle into the bronchial wall when the balloon is inflated, thus allowing direct therapeutic access to the bronchial adventitia. It has been discovered through Phase I research that broncho-adventitial delivery leads to cylindrical and longitudinal deposition of drugs around the bronchus, creating a natural drug-eluting reservoir. In this proposal, we hypothesize that by completing the development of the Mercator Micro-Infusion Catheter for bronchial use, we can show with statistical significance that local infusion of paclitaxel into the bronchial wall is safe for use in humans and effective at limiting airway occlusion in malignant disease. We intend to verify that the device can be used in bronchi up to 16 mm diameter while remaining compatible with the 2.8 mm working channel of bronchoscopes (Specific Aim 1). After this, we will statistically prove that bronchial delivery of paclitaxel is safe in animals and leads to long-term retention of chemotherapeutic doses (Specific Aim 2). Finally, we intend to show in a pilot human study that paclitaxel delivered to the airway wall can improve airway patency rates after malignant airway obstructions are removed (Specific Aim 3). We believe that the significance of this proposal lies in the facts that (a) we will test out a novel and innovative local drug delivery device for a recalcitrant clinical problem, (b) statistically showing a non-toxic dose of a common chemotherapeutic, anti-proliferative drug like paclitaxel can have broad-ranging clinical impact, (c) bronchial adventitial therapy may be more effective in the prevention and treatment of bronchial maladies than inhalation or systemic therapies and (d) therapeutic success in the delivery of paclitaxel for the treatment of bronchial carcinoma could be rapidly translated to other clinical settings of bronchial narrowing. Indeed, all of the above suggest a huge commercial potential for the Mercator product, if these pilot studies are successful.
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