title: Clinical evaluation of the delivery and safety of aerosolized liposomal 9-nitro-20(s)-camptothecin in patients with advanced pulmonary malignancies.
abstract: OBJECTIVE
  The purpose is to evaluate the feasibility and safety of aerosol administration of the topoisomerase I inhibitor, 9-nitrocamptothecin, in a liposome formulation, and to recommend a dosage for a Phase II trial for an 8-week daily treatment schedule.
  
  
  METHODS
  Patients with primary or metastatic lung cancer received aerosolized liposomal 9-nitrocamptothecin for 5 consecutive days/week for 1, 2, 4, or 6 weeks followed by 2 weeks of rest to determine feasibility. For the Phase I part, the dose was increased stepwise from 6.7 up to 26.6 micro g/kg/day Monday to Friday for 8 weeks followed by 2 weeks of rest.
  
  
  RESULTS
  Twenty-five patients received treatment. The mean baseline forced expiratory volume in 1 second for all patients was 85% of predicted. A dose-limiting toxicity was chemical pharyngitis seen after 1 week in 2 of 2 patients at 26.6 micro g/kg/day. At 20.0 micro g/kg/day, grade 2 and 3 fatigue prompting a dose reduction was seen after 4 weeks in 2 of 4 patients. Grade 2 toxic effects included nausea/vomiting (9 patients), cough and bronchial irritation (6 patients), fatigue (5 patients), anemia (4 patients), neutropenia (2 patients), anorexia (1 patient), and skin rash around the face mask (1 patient). 9-Nitro-20(S)-camptothecin (9NC) was absorbed systemically. Partial remissions were observed in 2 patients with uterine cancer, and stabilization occurred in 3 patients with primary lung cancer.
  
  
  CONCLUSIONS
  Aerosol administration of liposomal 9NC was found to be feasible and safe. 9NC delivered as an aerosol was detected in patient's plasma shortly after the start of treatment. The recommended dose for Phase II studies is 13.3 micro g/kg/day (equivalent to 0.5 mg/m(2)/day), which constitutes two consecutive 30-min nebulizations/day from a nebulizer reservoir with 4 mg of 9NC in 10 ml of sterile water, Monday to Friday for 8 weeks every 10 weeks.
authors.affiliation: Cancer Research and Treatment Center, University of New Mexico, Albequerque, New Mexico 87131, USA. cverschraegen@salud.unm.edu
authors.forename: Claire F
authors.initials: CF
authors.lastname: Verschraegen
authors.forename: Brian E
authors.initials: BE
authors.lastname: Gilbert
authors.forename: Evelyne
authors.initials: E
authors.lastname: Loyer
authors.forename: Armando
authors.initials: A
authors.lastname: Huaringa
authors.forename: Garrett
authors.initials: G
authors.lastname: Walsh
authors.forename: Robert A
authors.initials: RA
authors.lastname: Newman
authors.forename: Vernon
authors.initials: V
authors.lastname: Knight
mesh_terms: D000280:Administration, Inhalation; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002166:Camptothecin / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000494:pharmacology*; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008081:Liposomes / Q000378:metabolism*; D008113:Liver Neoplasms / Q000473:pathology; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D013997:Time Factors; D059003:Topoisomerase Inhibitors
chemical_list: D000970:Antineoplastic Agents; D008081:Liposomes; D059003:Topoisomerase Inhibitors; C079905:rubitecan; D002166:Camptothecin