Selective pulmonary artery perfusion for the treatment of primary lung cancer:Improved drug exposure of the lung

Introduction: Selective pulmonary artery perfusion (SPAP) is an experimental drug infusion method for the treatment of lung cancer that aims to achieve more effective T(umour) and lymph N(ode) down-staging. The aim of this experiment was to compare drug uptake of gemcitabine and carboplatin during SPAP and intravenous infusion (IV). Material and methods: SPAP was performed in 12 pigs using clinically applied doses of gemcitabine (1.25 g/m(2), n = 4) and carboplatin (AUC 5, n = 4) and a combination of both (n = 4). All animals underwent catheterisation of the left pulmonary artery and furthermore a left thoracotomy and lumbotomy for tissue sampling. After 2 min of SPAP, 30 min of blood flow occlusion was performed in order to delay drug washout from the lung. Two additional groups were infused intravenously (IV) using the same dose of gemcitabine (n = 4) and carboplatin (n = 4). Peak concentrations and area under the curve (AUC) were compared with t-tests. Results: Significantly higher pulmonary gemcitabine peak concentrations (p Conclusion: SPAP with gemcitabine and carboplatin resulted in significantly improved drug exposure of the lung compared to IV. Equivalent serum concentrations and a trend towards higher mediastinal lymph node concentrations were achieved for carboplatin. Summery: Selective pulmonary artery perfusion (SPAP) is an experimental drug infusion method for the treatment of lung cancer that aims to achieve more effective T(umour) and lymph N(ode) down-staging. The aim of this experiment was to compare drug uptake of gemcitabine and carboplatin during SPAP and intravenous infusion (IV). In conclusion, SPAP with carboplatin and gemcitabine or the combination of both showed a superior uptake profile into the lung while systemic exposure was equivalent compared to IV. Mediastinal lymph node concentrations are comparable with IV or tended to be higher after SPAP with carboplatin. (C) 2008 Elsevier Ireland Ltd. All rights reserved

Pharmacokinetics of gemcitabine when delivered by selective pulmonary artery perfusion for the treatment of lung cancer

Lung cancer represents a major health problem. Cytostatic and radiotherapeutic treatment is limited because of dose-limiting systemic toxicity and surgery as a result of its invasive nature. Therefore, we developed a catheterization model of selective pulmonary artery perfusion ( SPAP) combining the properties of isolated lung perfusion and i.v. treatment to achieve higher local drug levels and equivalent systemic exposure. Sixteen pigs underwent SPAP using a clinically applied dose of gemcitabine ( 1 g/m(2)). They furthermore underwent thoracotomy for tissue sampling. Three groups were treated with SPAP for 2 min with normal pulmonary blood flow, 50 and 90% flow reduction. Another group had SPAP for 10 min with normal blood flow. All the SPAP groups underwent catheterization of the left pulmonary artery. An additional group (n = 4) was infused i.v. for 30 min using the same dose. Concentrations were analyzed with analysis of variance. Pulmonary peak concentrations ( p = 0.01) and areas under the curve (AUC) ( p = 0.001) of SPAP for 2 and 10 min were significantly higher compared with i.v., whereas SPAP for 10 min resulted in the highest AUC ( p = 0.045) compared with SPAP for 2 min. Flow reduction during SPAP resulted in inhomogeneous distribution. Liver levels, AUC ( serum), and wet-to-dry ratios of all the SPAP groups were not significantly different compared with i.v. SPAP resulted in higher lung concentrations, whereas systemic exposure was comparable with i.v. Therefore, we advocate SPAP as a new method to be tested clinically to achieve down-staging of the tumor and lymph node status in lung cancer