title: Picoplatin pharmacokinetics and chemotherapy of non-small cell lung cancer.
abstract: BACKGROUND
  Picoplatin was developed as platinum coordination complex to overcome development of resistance, through conjugation to thioles, by the introduction of a methyl-pyridine moiety into the cisplatin parent structure. Pharmacokinetic parameters of the drug, after intravenous and oral application, were studied in solid tumors and clinical Phase I - III trials performed, in particular in NSCLC and small cell lung cancer (SCLC). Results showed low clinical activity of picoplatin.
  
  
  METHODS
  This article presents an overview of the pharmacokinetic assessments of picoplatin in lung cancer. Specifically, the authors address the relationship between disposition and clinical activity of the drug.
  
  
  CONCLUSIONS
  Picoplatin failed to overcome resistance to platinum compounds in lung cancer to achieve significant improved survival of most patients. Even highest doses of the drug reaching 150 m/m² given intravenously every 3 weeks were not sufficient to achieve better response than existing chemotherapeutics and the oral bioavailability of a dose of 200 - 400 mg corresponded only to 80 mg/m² iv. Picoplatin therefore seem to be quite ineffective. Picoplatin is expected to overcome tumor resistance in cases which overexpress thiol-conjugating pathways; however, this was not proved in clinical trials. To conclude, this blocked platinum complex is not able to reverse cisplatin resistance to a significant extent in vivo and its mechanisms and kinetics and of DNA damage failed to produce significant clinical results compared to second-line standard therapy for lung cancer.
authors.affiliation: Ludwig Boltzmann Cluster of Translational Oncology , c/o Balderichgasse 26/13, A-1170 Vienna , Austria +43 1 40400 6627 ; +43 1 40400 6627 ; Gerhard.hamilton@toc.lbg.ac.at.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Hamilton
authors.forename: Ulrike
authors.initials: U
authors.lastname: Olszewski
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000008:administration & dosage / Q000493:pharmacokinetics; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics*; D017671:Platinum Compounds / Q000493:pharmacokinetics; D016032:Randomized Controlled Trials as Topic
chemical_list: D009944:Organoplatinum Compounds; D017671:Platinum Compounds; C110525:amminedichloro(2-methylpyridine)platinum(II); D002945:Cisplatin