inhaled doxorubicin in treating patients with advanced solid tumors affecting the lungs

Conditions: Lung Cancer; Malignant Mesothelioma; Metastatic Cancer

Summary: rationale: drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. giving drugs in different ways may kill more tumor cells. purpose: phase i trial to study the effectiveness of inhaled doxorubicin in treating patients who have advanced solid tumors affecting the lungs.

objectives: * determine the maximum tolerated dose and phase ii dose of inhaled doxorubicin in patients with advanced solid tumors affecting the lungs. * determine the toxicity of this regimen in these patients. * determine the pharmacokinetic profile of inhaled doxorubicin in blood in these patients. * determine the relationship between pharmacodynamic parameters and toxic effects of this regimen in these patients. outline: this is a dose-escalation study. patients receive inhaled doxorubicin every 3 weeks for up to 3 doses. patients with stable or responding disease may receive additional doses in the absence of disease progression or unacceptable toxicity. cohorts of 3-6 patients receive escalating doses of doxorubicin until the maximum tolerated dose (mtd) is determined. the mtd is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. patients are followed at 3 weeks and 3 months. projected accrual: approximately 33 patients will be accrued for this study within 18-24 months.

Eligibility criteria:
disease characteristics: * histologically proven advanced cancer not curable by standard chemotherapy, radiotherapy, or surgery * clinical evidence of primary lung or tracheal cancer or * metastatic cancer to the lung * extrathoracic metastases eligible if following criteria are met: * sites are stable * pulmonary sites are primary life-threatening sites * evidence that study treatment may benefit the patient * measurable or evaluable disease * no germ cell tumor, leukemia, or lymphoma involving the lungs that is treatable with systemic agents * no complete atelectasis due to high-grade airway obstruction patient characteristics: age: * 18 and over performance status: * ecog 0-1 life expectancy: * more than 3 months hematopoietic: * absolute neutrophil count at least 1,500/mm\^3 * platelet count at least 100,000/mm\^3 * hemoglobin at least 10 g/dl hepatic: * bilirubin no greater than 1.0 mg/dl * ast and alt less than 1.5 times upper limit of normal renal: * creatinine no greater than 1.6 mg/dl or * creatinine clearance at least 60 ml/min cardiovascular: * lvef at least 40% by muga scan or echocardiogram * no unstable angina, congestive heart failure, or symptomatic arrhythmias pulmonary: * dlco at least 50% predicted * fvc and fev1 at least 50% predicted * resting oxygen saturation at least 90% * exercise oxygen saturation at least 85% * oxygen consumption greater than 50% predicted * no prior radiation pneumonitis * no asthma * no radiation-induced pulmonary damage other: * no hypersensitivity to doxorubicin * not pregnant or nursing * negative pregnancy test * fertile patients must use effective contraception during and for 6 months after study * hiv negative * no congenital problems (e.g., cleft palate) or other anomalies that prevent tight fit of a mouthseal prior concurrent therapy: biologic therapy: * at least 4 weeks since prior biologic therapy and recovered * no prior trastuzumab (herceptin) chemotherapy: * see disease characteristics * at least 4 weeks since prior chemotherapy and recovered * prior doxorubicin allowed if lvef at least 40% by muga scan or echocardiogram * no prior mitomycin, bleomycin, or nitrosoureas * no other concurrent systemic chemotherapy endocrine therapy: * not specified radiotherapy: * see disease characteristics * at least 4 weeks since prior radiotherapy and recovered * at least 12 months since prior radiotherapy to chest * no prior radiotherapy to more than 20% of total lung volume * prior chest wall or primary breast radiotherapy allowed * prior radioactive iodine allowed * no concurrent thoracic radiotherapy surgery: * see disease characteristics * no prior total pneumonectomy other: * no other concurrent experimental drug

Keywords: recurrent non-small cell lung cancer extensive stage small cell lung cancer recurrent small cell lung cancer advanced malignant mesothelioma recurrent malignant mesothelioma stage iiib non-small cell lung cancer stage iv non-small cell lung cancer pulmonary carcinoid tumor lung metastases