Pleural effusion is the accumulation of fluid between the chest wall and the lung. Malignant pleural effusion (MPE) occurs secondary to metastatic malignancy to the pleural surface. Approximately 200,000 patients a year in the United States develop MPE. MPE substantially affects the quality of life for these advanced cancer patients. The treatment of choice for approximately 50,000 of these patients is pleurodesis. Pleurodesis is the obliteration of the potential pleural space. This obliteration is typically done by the administration of a scleroscent. These compounds currently fall in to two categories, irritants or cytotoxins. The FDA currently approves one compound in each category, talc or bleomycin respectively, for pleurodesis. It is assumed that each of these reagents acts through an inflammatory mechanism. Neither of these is without side effects. Both are less than 80% effective. Talc carries a small, but real, risk of sudden respiratory failure following administration. Bleomycin is less effective than talc and can be extremely painful. Because the endpoint of pleurodesis is a fibrotic fusion of the parietal and visceral pleura, the investigators have chosen to investigate a non-inflammatory mechanism to induce a pleurodesis. TGF-beta is a well-known fibrogenic growth factor. In pilot studies the investigators have shown that the administration of TGF-beta creates an effective pleurodesis in rabbits. The pleura of the sheep is a much more suitable model of the human pleura. In a single experiment an effective pleurodesis was achieved in sheep. These preliminary data are compelling to initiate an animal study to compare the accepted plurodesants with TGF-beta. The therapeutic use of TGF-beta is currently being explored for diabetic foot ulcers in phase II/III trials. Pleurodesis would be a new indication for this compound.
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