Phase I/II Study of Inhaled Doxorubicin Combined with Platinum-Based Therapy for Advanced Non–Small Cell Lung Cancer

Abstract

Purpose: We have shown the feasibility of administering inhaled doxorubicin to patients with cancer. This study evaluated inhaled doxorubicin combined with cisplatin and docetaxel in patients with non–small cell lung cancer. The principal objective was to determine safety and, secondarily, efficacy. Experimental Design: Patients who had chemo-naïve advanced non–small cell lung cancer were enrolled in the study. Adequate organ and pulmonary function was required: diffusing capacity for carbon monoxide/forced expiratory volume in 1 second/forced vital capacity ≥50%, resting/exercise O₂ saturation ≥90%/85%. In phase I, doxorubicin was escalated: dose level 1 (6 mg/m²) and level 2 (7.5 mg/m²). Escalation was permitted if ≤2 of 6 patients experienced pulmonary dose-limiting toxicity (grade 2 Radiation Therapy Oncology Group lung morbidity; resting O₂ saturation of 2. Treatments and pulmonary function tests were repeated every 21 days, with up to eight cycles for responding patients. Results: Twenty-eight patients were treated at level 1 and eight patients at level 2. Doxorubicin was escalated to 7.5 mg/m², however, after two patients developed pulmonary dose-limiting toxicity; the remainder were treated at 6.0 mg/m². Twenty-four evaluable patients received at least two courses or had progressive disease following the first course at the phase II dose. Toxicity was associated with i.v. chemotherapy although one patient had delayed pulmonary toxicity responding to corticosteroids and oxygen. Seven (29%) evaluable patients responded (six partial responses and one complete response) and 13 (54%) patients had stable disease for up to eight cycles. Conclusion: Although this combination was safe, the primary objective was not met and will not be pursued further. Clin Cancer Res; 16(8); 2466–73. ©2010 AACR.