PURPOSE: To evaluate the toxicity profile of inhalational doxorubicin in patients with malignant disease in the lung. EXPERIMENTAL DESIGN: 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.
PURPOSE: To evaluate the toxicity profile of inhalational doxorubicin in patients with malignant disease in the lung. EXPERIMENTAL DESIGN: 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: Rachel Yoon Kyung Chang; Philip Chi Lip Kwok; Sussan Ghassabian; John D Brannan; Heikki O Koskela; Hak-Kim Chan Journal: Br J Pharmacol Date: 2020-08-07 Impact factor: 8.739
Authors: Gemma M Ryan; Robert J Bischof; Perenlei Enkhbaatar; Victoria M McLeod; Linda J Chan; Seth A Jones; David J Owen; Christopher J H Porter; Lisa M Kaminskas Journal: Pharm Res Date: 2015-10-20 Impact factor: 4.200
Authors: Susanne R Youngren-Ortiz; David B Hill; Peter R Hoffmann; Kenneth R Morris; Edward G Barrett; M Gregory Forest; Mahavir B Chougule Journal: J Aerosol Med Pulm Drug Deliv Date: 2017-03-09 Impact factor: 2.849
Authors: James Verco; William Johnston; Michael Baltezor; Philip J Kuehl; Andrew Gigliotti; Steven A Belinsky; Anita Lopez; Ronald Wolff; Lauren Hylle; Gere diZerega Journal: J Aerosol Med Pulm Drug Deliv Date: 2018-10-25 Impact factor: 2.849