title: Optimized intrapleural cisplatin chemotherapy with a fibrin carrier after extrapleural pneumonectomy: a preclinical study.
abstract: OBJECTIVE
  Our objective was to evaluate whether platinum concentrations in chest wall tissue and in serum are optimized by intracavitary application of cisplatin loaded to a fibrin carrier compared with cisplatin solution in a randomized setting of a pig model.
  
  
  METHODS
  After left-sided pneumonectomy including parietal pleurectomy, pigs were randomly assigned to receive either 90 mg/m(2) cisplatin intracavitary solution (n = 6) or to receive 5 mg cisplatin-fibrin (n = 5) applied on a predefined area of the chest wall. Platinum concentration in serum as well as in chest wall tissue was determined at several early time points until day 5 after treatment. Platinum levels were measured by inductively coupled plasma sector field mass spectrometric detection with a matrix-matched calibration procedure.
  
  
  RESULTS
  The dose- and surface-corrected (geometric) mean concentration of cisplatin in chest wall tissue 2 hours but also at day 5 after the application was doubled in animals treated with cisplatin-fibrin compared with the animals treated with cisplatin-solution. In serum, the dose- and surface-corrected exposure toward cisplatin (area under the curve(0-5d)) was significantly lower with cisplatin-fibrin than with cisplatin-solution (P < .0005). This is also reflected by significantly reduced serum creatinine and urea values in the cisplatin-fibrin group (P < .0001). Animals treated with cisplatin-fibrin additionally had a significantly better postoperative course as assessed by a well-being score (P < .001).
  
  
  CONCLUSIONS
  After cisplatin-fibrin treatment, cisplatin tissue concentration was increased whereas systemic cisplatin concentrations were significantly reduced in comparison with cisplatin-solution treatment. This finding offers a clear advantage inasmuch as rate and severity of systemic adverse events can be reduced while local cytotoxic concentrations are at least maintained.
authors.affiliation: Division of Thoracic Surgery, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Opitz
authors.forename: Barbara V
authors.initials: BV
authors.lastname: Erne
authors.forename: Seval
authors.initials: S
authors.lastname: Demirbas
authors.forename: Alexander
authors.initials: A
authors.lastname: Jetter
authors.forename: Burkhardt
authors.initials: B
authors.lastname: Seifert
authors.forename: Rolf
authors.initials: R
authors.lastname: Stahel
authors.forename: Walter
authors.initials: W
authors.lastname: Weder
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity; D015415:Biomarkers / Q000097:blood; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity; D003404:Creatinine / Q000097:blood; D004333:Drug Administration Routes; D004337:Drug Carriers; D015718:Fibrin Tissue Adhesive; D023421:Models, Animal; D035422:Pleural Cavity; D011013:Pneumonectomy / Q000379:methods*; D013054:Spectrophotometry, Atomic; D034421:Sus scrofa; D035441:Thoracic Wall / Q000378:metabolism; D014018:Tissue Distribution
chemical_list: D000970:Antineoplastic Agents; D015415:Biomarkers; D004337:Drug Carriers; D015718:Fibrin Tissue Adhesive; D003404:Creatinine; D002945:Cisplatin