Drug-eluting Tracheobronchial Stents to treat Obstruction caused by Lung Cancer

DESCRIPTION (provided by applicant): Airways can be obstructed by a variety of diseases resulting in breathing difficulties and compromised quality of life for the patients. Lung cancer is one of the major diseases causing airway obstruction. According to the American Cancer Society it is the single largest cause of cancer deaths in the United States (173,000 estimated new cases diagnosed in 2006) and more than 160,000 people will die of the disease each year mostly due to delayed diagnosis. Worldwide more than 1.2 million new cases of lung and bronchial cancer are diagnosed each year worldwide, causing approximately 1.1 million deaths annually. Approximately 30% of the symptomatic lung cancer patients will present with an airway obstruction requiring local tumor control with endobronchial interventions. Palliative reopening of the affected airways often alleviates symptoms such as dyspnea, cough, or hemoptysis. Endobronchial interventions provide rapid relief of symptoms, improved quality of life, and may indirectly prolong survival by allowing patients to undergo chemo and/or radiation therapy. Our objective is to develop drug or combination drugs-eluting stent (DES) as a multi- modal adjunct intervention to treat airway obstruction caused due to lung cancer. By virtue of targeting multiple processes (physical and biological/molecular) in conjunction with laser or electrosurgery, the drug(s)-eluting stent has the potential of being superior to any single endobronchial intervention including a regular stent. AraVasc plans to address the need for a superior stent by developing a drug or combination drugs eluting self-expanding metallic stent. The drugs chosen are multi- targeted and have proven anti-tumor activity agains lung cancer. The overall objective of the Phase I project is to demonstrate the feasibility of developing a biodegradable polymeric formulation of drug(s) coated on a self-expanding metallic stent. The specific objectives of this proposal are: 1. Develop preclinical animal-stents to enable proof-of-concept drug uptake and distribution studies in rats. 2. Develop methods to test the performance of the stents 3. Conduct intra-tracheal pharmacokinetic studies to estimate drug uptake and tissue distribution in the local tracheo-bronchial and lung area. 4. Develop and coat 3 prototype biodegradable polymer-drug(s) formulations on a representative tracheo-bronchial stent. The proposed drug-eluting tracheo-bronchial stent is designed to treat obstructions caused by lung cancer. It is beneficial for public health because it is predicted to improve the overall quality of life of advanced lung cancer patients by providing immediate palliative relief from the symptoms of obstructed airways such as coughing, choking, inability to eat, etc. It is predicted to provide both acute symptomatic relief by virtue of it's physical strength and long term benefits by virtue of the drug acting on the airway- encroaching tumor cells and on local tissue hyperplasia thus allowing time for other anti- cancer therapies to work and improve survival times.