Phase I study of inhaled doxorubicin for patients with metastatic tumors to the lungs

Gregory A. Otterson, Miguel A. Villalona-Calero, Sunil Sharma, Mark G. Kris, Anthony Imondi, Mirjam Gerber, Dorothy A. White, Mark J. Ratain, Joan H. Schiller, Alan Sandler, Michael Kraut, Sridhar Mani, John R. Murren

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Abstract

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 μm 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 SaO2 >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/m2 dose level when two of four patients experienced pulmonary DLT. Of 11 patients treated at the 7.5 mg/m2 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/m2 every 3 weeks in patients with cancer who had normal to moderately impaired pulmonary function.

Original languageEnglish (US)
Pages (from-to)1246-1252
Number of pages7
JournalClinical Cancer Research
Volume13
Issue number4
DOIs
StatePublished - Feb 15 2007

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Doxorubicin
Lung
Neoplasms
Vital Capacity
Sarcoma
Ifosfamide
Nebulizers and Vaporizers
Respiratory Function Tests
Technetium
Forced Expiratory Volume
Carbon Monoxide
Drug-Related Side Effects and Adverse Reactions
Aerosols
Non-Small Cell Lung Carcinoma
Lung Diseases
Research Design

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Otterson, G. A., Villalona-Calero, M. A., Sharma, S., Kris, M. G., Imondi, A., Gerber, M., ... Murren, J. R. (2007). Phase I study of inhaled doxorubicin for patients with metastatic tumors to the lungs. Clinical Cancer Research, 13(4), 1246-1252. https://doi.org/10.1158/1078-0432.CCR-06-1096

Phase I study of inhaled doxorubicin for patients with metastatic tumors to the lungs. / Otterson, Gregory A.; Villalona-Calero, Miguel A.; Sharma, Sunil; Kris, Mark G.; Imondi, Anthony; Gerber, Mirjam; White, Dorothy A.; Ratain, Mark J.; Schiller, Joan H.; Sandler, Alan; Kraut, Michael; Mani, Sridhar; Murren, John R.

In: Clinical Cancer Research, Vol. 13, No. 4, 15.02.2007, p. 1246-1252.

Research output: Contribution to journalArticle

Otterson, GA, Villalona-Calero, MA, Sharma, S, Kris, MG, Imondi, A, Gerber, M, White, DA, Ratain, MJ, Schiller, JH, Sandler, A, Kraut, M, Mani, S & Murren, JR 2007, 'Phase I study of inhaled doxorubicin for patients with metastatic tumors to the lungs', Clinical Cancer Research, vol. 13, no. 4, pp. 1246-1252. https://doi.org/10.1158/1078-0432.CCR-06-1096
Otterson GA, Villalona-Calero MA, Sharma S, Kris MG, Imondi A, Gerber M et al. Phase I study of inhaled doxorubicin for patients with metastatic tumors to the lungs. Clinical Cancer Research. 2007 Feb 15;13(4):1246-1252. https://doi.org/10.1158/1078-0432.CCR-06-1096
Otterson, Gregory A. ; Villalona-Calero, Miguel A. ; Sharma, Sunil ; Kris, Mark G. ; Imondi, Anthony ; Gerber, Mirjam ; White, Dorothy A. ; Ratain, Mark J. ; Schiller, Joan H. ; Sandler, Alan ; Kraut, Michael ; Mani, Sridhar ; Murren, John R. / Phase I study of inhaled doxorubicin for patients with metastatic tumors to the lungs. In: Clinical Cancer Research. 2007 ; Vol. 13, No. 4. pp. 1246-1252.
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abstract = "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 μm 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 SaO2 >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/m2 dose level when two of four patients experienced pulmonary DLT. Of 11 patients treated at the 7.5 mg/m2 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/m2 every 3 weeks in patients with cancer who had normal to moderately impaired pulmonary function.",
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AU - Gerber, Mirjam

AU - White, Dorothy A.

AU - Ratain, Mark J.

AU - Schiller, Joan H.

AU - Sandler, Alan

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AU - Mani, Sridhar

AU - Murren, John R.

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N2 - 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 μm 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 SaO2 >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/m2 dose level when two of four patients experienced pulmonary DLT. Of 11 patients treated at the 7.5 mg/m2 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/m2 every 3 weeks in patients with cancer who had normal to moderately impaired pulmonary function.

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