Phase I study of inhaled Doxorubicin for patients with metastatic tumors to the lungs.
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.
Otterson
Gregory A
GA
The Ohio State University Comprehensive Cancer Center, Columbus, Ohio, USA. greg.otterson@osumc.edu
Villalona-Calero
Miguel A
MA
Sharma
Sunil
S
Kris
Mark G
MG
Imondi
Anthony
A
Gerber
Mirjam
M
White
Dorothy A
DA
Ratain
Mark J
MJ
Schiller
Joan H
JH
Sandler
Alan
A
Kraut
Michael
M
Mani
Sridhar
S
Murren
John R
JR
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
D000336:Aerosols; D000903:Antibiotics, Antineoplastic; D004317:Doxorubicin