Introduction: Lung cancer represents a major health problem. Cytostatic and radio-therapeutic treatment are both limited due to dose-limiting systemic toxicity and surgery due to its invasive nature respectively. Therefore, we developed a catheterisation model of selective pulmonary artery perfusion (SPAP) combining the properties of isolated lung perfusion and intravenous treatment to achieve higher local drug levels and equivalent systemic exposure.
Material and Methods: Sixteen pigs underwent SPAP using a clinically applied dose of gemcitabine (1g/m2). They furthermore underwent thoracotomy for tissue sampling. Three groups were treated with SPAP for two minutes with normal pulmonary blood flow, 50% and 90% flow reduction. Another group had SPAP for ten minutes with normal blood flow. All SPAP groups underwent catheterisation of the left pulmonary artery. An additional group (n=4) was infused intravenously (IV) for thirty minutes using the same dose. Concentrations were compared with ANOVA analysis.
Results: Pulmonary peak concentrations (p=0.01) and areas under the curve (AUC) (p=0.001) of SPAP for two and ten minutes were significantly higher compared to IV while SPAP for ten minutes resulted in the highest AUC (p=0.045) compared to SPAP for two minutes. Flow reduction during SPAP resulted in inhomogeneous distribution. Liver levels, AUC (serum) and wet-to-dry ratios of all SPAP groups were not significantly different compared to IV.
Conclusion: SPAP resulted in higher lung concentrations while systemic exposure was comparable with IV. Therefore, we advocate SPAP as a new method to be tested in a phase 1 trial to achieve more effective local control of lung cancer.