Phase I study of inhaled doxorubicin for patients with metastatic tumors to the lungs Journal Article
| Authors: | Otterson, G. A.; Villalona-Calero, M. A.; Sharma, S.; Kris, M. G.; Imondi, A.; Gerber, M.; White, D. A.; Ratain, M. J.; Schiller, J. H.; Sandler, A.; Kraut, M.; Mani, S.; Murren, J. R. |
| Article Title: | Phase I study of inhaled doxorubicin for patients with metastatic tumors to the lungs |
| 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. © 2007 American Association for Cancer Research. |
| Keywords: | adult; controlled study; human tissue; treatment response; aged; middle aged; major clinical study; clinical trial; fatigue; histopathology; doxorubicin; area under the curve; cancer growth; dose response; drug efficacy; drug safety; side effect; technetium 99m; anorexia; nutritional status; controlled clinical trial; lung toxicity; multiple cycle treatment; bone marrow suppression; blood toxicity; lung non small cell cancer; mucosa inflammation; nausea; lung neoplasms; antineoplastic activity; dose-response relationship, drug; ifosfamide; coughing; drug dose escalation; dyspnea; loading drug dose; rash; hypoxia; drug fatality; lung metastasis; thorax pain; device; neoplasm metastasis; taste disorder; soft tissue sarcoma; blood pressure; optimal drug dose; phase 1 clinical trial; antibiotics, antineoplastic; dyspepsia; heart left ventricle ejection fraction; forced expiratory volume; alopecia; lung function test; maximum allowable concentration; dose calculation; congestive heart failure; oxygen saturation; lung infiltrate; tachycardia; drug delivery system; particle size; bronchospasm; mouth pain; sore throat; hemoptysis; hoarseness; carbon monoxide; wheezing; lung diffusion capacity; sweating; eosinophilia; lung sarcoma; respiratory distress; salivation; vital capacity; aerosol; exhalation; administration, inhalation; aerosols |
| Journal Title: | Clinical Cancer Research |
| Volume: | 13 |
| Issue: | 4 |
| ISSN: | 1078-0432 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2007-02-15 |
| Start Page: | 1246 |
| End Page: | 1252 |
| Language: | English |
| DOI: | 10.1158/1078-0432.ccr-06-1096 |
| PUBMED: | 17317836 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 19" - "Export Date: 17 November 2011" - "CODEN: CCREF" - "Source: Scopus" |
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