title: Aerosolized gemcitabine in patients with carcinoma of the lung: feasibility and safety study.
abstract: BACKGROUND
  We investigated the biodistribution, pharmacokinetics, safety profile, and feasibility of aerosolized gemcitabine (GCB) in patients with lung carcinoma.
  
  
  METHODS
  Eleven patients with carcinoma localized in the lungs were studied in a dose escalation study of aerosolized GCB administered 1 day/week for 9 consecutive weeks. Safety data, scintigraphic assessment of the delivered dose and pharmacokinetic monitoring were analyzed. Patients were treated with doses of between 1 mg/kg and 4 mg/kg (dose in the nebulizer), using a new inhaler device (Aeroneb Pro with an Idehaler Chamber).
  
  
  CONCLUSIONS
  The total dose of GCB delivered to the patient's lung was 42±16% of the initial amount of dose in the nebulizer. Safety data showed no hematologic toxicity, nephrotoxicity or neurotoxicity. At 4 mg/kg, one patient experienced grade 4 pulmonary toxicity (bronchospasm), which was the dose-limiting toxicity. Grade 2 and 3 toxic effects included fatigue, vomiting, dyspnea, and cough. Overall response: minor response in one patient, stable disease in four patients, progressive disease in four patients. Pharmacokinetic data showed very low plasma GCB levels. Maximal plasma concentration was observed at the end of nebulization. Aerosolized gemcitabin was safe, with minimal toxicity, for patients with lung carcinoma.
authors.affiliation: INSERM U 618, IFR135, Bretonneau University Hospital, François Rabelais University, Tours, France. lemarie@med.univ-tours.fr
authors.forename: Etienne
authors.initials: E
authors.lastname: Lemarie
authors.forename: Laurent
authors.initials: L
authors.lastname: Vecellio
authors.forename: Jose
authors.initials: J
authors.lastname: Hureaux
authors.forename: Caroline
authors.initials: C
authors.lastname: Prunier
authors.forename: Chantal
authors.initials: C
authors.lastname: Valat
authors.forename: Daniel
authors.initials: D
authors.lastname: Grimbert
authors.forename: Michele
authors.initials: M
authors.lastname: Boidron-Celle
authors.forename: Bruno
authors.initials: B
authors.lastname: Giraudeau
authors.forename: Alain
authors.initials: A
authors.lastname: le Pape
authors.forename: Eric
authors.initials: E
authors.lastname: Pichon
authors.forename: Patrice
authors.initials: P
authors.lastname: Diot
authors.forename: Abder
authors.initials: A
authors.lastname: el Houfia
authors.forename: Frederic
authors.initials: F
authors.lastname: Gagnadoux
mesh_terms: D000336:Aerosols; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000503:physiopathology; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D005240:Feasibility Studies; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D000093542:Gemcitabine
chemical_list: D000336:Aerosols; D000964:Antimetabolites, Antineoplastic; D003841:Deoxycytidine; D000093542:Gemcitabine