title: Phase I study of aerosolized SLIT cisplatin in the treatment of patients with carcinoma of the lung.
abstract: OBJECTIVE
  To investigate the safety and pharmacokinetics of aerosolized Sustained Release Lipid Inhalation Targeting (SLIT) Cisplatin in patients with lung carcinoma.
  
  
  METHODS
  Phase I, dose-escalating study of SLIT Cisplatin given in two sessions daily. Safety data, including laboratory variables, adverse events, pulmonary function tests, and radiographic imaging, were collected and analyzed for all patients to determine toxicity. Pharmacokinetic monitoring was done during the first course.
  
  
  RESULTS
  Seventeen patients and one tracheostomy patient on compassionate use received treatment. Aerosolized cisplatin was well tolerated. No dose-limiting toxicity was observed at the maximum delivered dose. Safety data showed no hematologic toxicity, nephrotoxicity, ototoxicity, or neurotoxicity. Most common adverse events were nausea (64.7%), vomiting (47.1%), dyspnea (64.7%), fatigue (64.7%), and hoarseness (47.1%). Pharmacokinetic data showed very low plasma platinum levels only with the longest repeated inhalations. Common Toxicity Criteria grade 2 decrease in forced expiratory volume in one second and diffusing lung capacity for carbon monoxide after one course occurred both in two patients and grade one decrease in forced expiratory volume in one second and diffusing lung capacity for carbon monoxide in six and five patients, respectively. Direct airway deposition via the tracheostomy resulted in clinical deterioration after two cycles best described as bronchitis, completely reversible within days. Overall response: stable disease in 12 patients and progressive disease in 4 patients (one patient received one cycle).
  
  
  CONCLUSIONS
  Aerosolized liposomal cisplatin was found to be feasible and safe.
authors: Department of Pulmonary Diseases, VU University Medical Center, Amsterdam, the Netherlands.
authors: Bart P H
authors: BP
authors: Wittgen
authors: Peter W A
authors: PW
authors: Kunst
authors: Kasper
authors: K
authors: van der Born
authors: Atie W
authors: AW
authors: van Wijk
authors: Walter
authors: W
authors: Perkins
authors: Frank G
authors: FG
authors: Pilkiewicz
authors: Roman
authors: R
authors: Perez-Soler
authors: Susan
authors: S
authors: Nicholson
authors: Godefridus J
authors: GJ
authors: Peters
authors: Pieter E
authors: PE
authors: Postmus
mesh_terms: D000280:Administration, Inhalation; D000328:Adult; D000336:Aerosols; D000368:Aged; D000970:Antineoplastic Agents / Q000633:toxicity; D002945:Cisplatin / Q000008:administration & dosage / Q000633:toxicity*; D003692:Delayed-Action Preparations; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D008875:Middle Aged; D012449:Safety
chemical_list: D000336:Aerosols; D000970:Antineoplastic Agents; D003692:Delayed-Action Preparations; D002945:Cisplatin