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

被引:107
作者
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.
机构
[1] Ohio State Univ, Div Hematol Oncol, Ctr Comprehens Canc, Columbus, OH 43210 USA
[2] Zivena Inc, Columbus, OH USA
[3] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA
[4] Univ Chicago, Chicago, IL 60637 USA
[5] Univ Wisconsin, Ctr Canc, Madison, WI USA
[6] Vanderbilt Univ, Med Ctr, Nashville, TN USA
[7] Karmanos Canc Ctr, Detroit, MI USA
[8] Montefiore Med Ctr, Weiler Div, Bronx, NY 10467 USA
[9] Yale Univ, Ctr Comprehens Canc, New Haven, CT USA
关键词
D O I
10.1158/1078-0432.CCR-06-1096
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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 mu m 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.
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收藏
页码:1246 / 1252
页数:7
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