Isolated lung perfusion with melphalan: pharmacokinetics and XXXX in a @entity1707 model.

@entity1 @entity1707 @entity697 @entity137 @entity3126 @entity2
BACKGROUND: In @entity1 with unresectable @entity2 or pulmonary metastases, isolated lung perfusion (ILP) has been described as an alternative method to deliver high-dose chemotherapy to the lungs, thereby minimizing systemic @entity137 . Pharmacokinetics of ILP have not been extensively investigated. Therefore, we studied the feasibility of ILP with melphalan in a @entity1707 model with emphasis on pharmacokinetics and @entity697 . METHODS: Five @entity1707 underwent ILP with melphalan. Blood and tissue samples were obtained for determination of melphalan levels. Tissue biopsies were taken for microscopic evaluation of lung damage. RESULTS: During ILP, no hemodynamic effects of importance were noted. No systemic leakage of melphalan was observed in any of the animals. Compared with normal lung tissue, microscopic examination of lung tissue after perfusion without melphalan showed @entity3126 . Directly after melphalan perfusion additional hemorrhagic areas were seen; however, electron microscopy displayed no irreversible endothelial damage. CONCLUSION: This study on @entity1707 proved to be a well reproducible model for ILP with melphalan. Pharmacokinetics show a safety profile with no systemic @entity137 , which could justify further @entity1 studies, necessary to determine its effect on pulmonary metastases in @entity1 , especially in case of adjuvant therapy after surgical resection or in unresectable disease.
