title: Phase I study of inhaled Doxorubicin for patients with metastatic tumors to the lungs.
abstract: OBJECTIVE
  To evaluate the toxicity profile of inhalational doxorubicin in patients with malignant disease in the lung.
  
  
  METHODS
  The OncoMyst Model CDD-2a inhalation device aerosolizes compounds to particles of 2 to 3 mum and prevents exhaled aerosol from escaping into the environment. Deposition efficiency of inhaled Technetium 99m was used to predict deposition of doxorubicin and calculate dose. Treatment was repeated every 3 weeks. No more than moderate pulmonary dysfunction was permitted (forced expiratory volume in 1 s, forced vital capacity, and diffusing capacity for carbon monoxide, all >50% predicted; resting SaO(2) >90%).
  
  
  RESULTS
  Fifty-three patients were enrolled at 13 dose levels ranging from 0.4 to 9.4 mg/m(2). The most common histologic diagnoses were sarcoma (n = 19) and non-small cell lung cancer (n = 16). Dose-limiting toxicity (DLT) was observed at the 9.4 mg/m(2) dose level when two of four patients experienced pulmonary DLT. Of 11 patients treated at the 7.5 mg/m(2) dose level, only one showed DLT consisting of a decline in forced vital capacity of >20% from baseline. No significant systemic drug-related toxicity was observed. Several patients experienced declines in pulmonary function test variables, which were attributed to progressive disease. Observed activity included a partial response in a patient with metastatic soft tissue sarcoma previously treated with i.v. doxorubicin and ifosfamide.
  
  
  CONCLUSIONS
  Inhaled doxorubicin is safe up to a dose of 7.5 mg/m(2) every 3 weeks in patients with cancer who had normal to moderately impaired pulmonary function.
authors.affiliation: The Ohio State University Comprehensive Cancer Center, Columbus, Ohio, USA. greg.otterson@osumc.edu
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Otterson
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Villalona-Calero
authors.forename: Sunil
authors.initials: S
authors.lastname: Sharma
authors.forename: Mark G
authors.initials: MG
authors.lastname: Kris
authors.forename: Anthony
authors.initials: A
authors.lastname: Imondi
authors.forename: Mirjam
authors.initials: M
authors.lastname: Gerber
authors.forename: Dorothy A
authors.initials: DA
authors.lastname: White
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Ratain
authors.forename: Joan H
authors.initials: JH
authors.lastname: Schiller
authors.forename: Alan
authors.initials: A
authors.lastname: Sandler
authors.forename: Michael
authors.initials: M
authors.lastname: Kraut
authors.forename: Sridhar
authors.initials: S
authors.lastname: Mani
authors.forename: John R
authors.initials: JR
authors.lastname: Murren
mesh_terms: D000280:Administration, Inhalation; D000328:Adult; D000336:Aerosols / Q000008:administration & dosage; D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000009:adverse effects* / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage* / Q000009:adverse effects* / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000556:secondary*; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis
chemical_list: D000336:Aerosols; D000903:Antibiotics, Antineoplastic; D004317:Doxorubicin