title: Selective pulmonary artery perfusion for the treatment of primary lung cancer: Improved drug exposure of the lung.
abstract: BACKGROUND
  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).
  
  
  METHODS
  SPAP was performed in 12 pigs using clinically applied doses of gemcitabine (1.25g/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 2min of SPAP, 30min 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<or=0.017) and AUC (p<or=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<or=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 10min compared to IV carboplatin (p=0.04).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Cardio-thoracic Surgery, Sint Antonius Hospital, Koekoekslaan 1, Nieuwegein, The Netherlands. bvanputte@yahoo.com
authors.forename: Bart P
authors.initials: BP
authors.lastname: van Putte
authors.forename: Marco
authors.initials: M
authors.lastname: Grootenboers
authors.forename: Wim-Jan
authors.initials: WJ
authors.lastname: van Boven
authors.forename: M
authors.initials: M
authors.lastname: van Oosterhout
authors.forename: Gerard
authors.initials: G
authors.lastname: Pasterkamp
authors.forename: Gert
authors.initials: G
authors.lastname: Folkerts
authors.forename: Franz
authors.initials: F
authors.lastname: Schramel
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D019540:Area Under Curve; D016190:Carboplatin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D010478:Chemotherapy, Cancer, Regional Perfusion / Q000379:methods*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D005260:Female; D008175:Lung Neoplasms / Q000188:drug therapy*; D013552:Swine; D000093542:Gemcitabine
chemical_list: D000970:Antineoplastic Agents; D003841:Deoxycytidine; D016190:Carboplatin; D000093542:Gemcitabine