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

Abstract

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 ≤ 0.017) and AUC ( p ≤ 0.020) were observed after SPAP gemcitabine and gemcitabine/carboplatin compared to IV while no differences were shown between serum, renal and lymph tissue. Furthermore, SPAP carboplatin and gemcitabine/carboplatin also resulted in significantly higher pulmonary carboplatin peak concentrations ( p ≤ 0.018) compared to IV while AUC was significantly higher after SPAP gemcitabine/carboplatin ( p = 0.045). SPAP carboplatin resulted in significantly higher lymph concentrations at 10 min compared to IV carboplatin ( p = 0.04). 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.