Phase I/II study of inhaled doxorubicin combined with platinum-based therapy for advanced non-small cell lung cancer.
OBJECTIVE
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.


METHODS
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 > or =50%, resting/exercise O(2) saturation > or =90%/85%. In phase I, doxorubicin was escalated: dose level 1 (6 mg/m(2)) and level 2 (7.5 mg/m(2)). Escalation was permitted if < or =2 of 6 patients experienced pulmonary dose-limiting toxicity (grade 2 Radiation Therapy Oncology Group lung morbidity; resting O(2) saturation of <85%; decrease in diffusing capacity for carbon monoxide, forced vital capacity, or forced expiratory volume in 1 second of > or =20% from baseline or < or =30% of predicted; or grade 3 Common Terminology Criteria for Adverse Events version 3.0 pulmonary toxicity). Doses of cisplatin and docetaxel were 75 mg/m(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/m(2), however, after two patients developed pulmonary dose-limiting toxicity; the remainder were treated at 6.0 mg/m(2). 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.


CONCLUSIONS
Although this combination was safe, the primary objective was not met and will not be pursued further.
Otterson
Gregory A
GA
Comprehensive Cancer Center and Center for Biostatistics, The Ohio State University, Columbus, Ohio, USA. greg.otterson@osumc.edu
Villalona-Calero
Miguel A
MA
Hicks
William
W
Pan
Xueliang
X
Ellerton
John A
JA
Gettinger
Scott N
SN
Murren
John R
JR
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000280:Administration, Inhalation; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D018287:Carcinoma, Large Cell / Q000188:drug therapy* / Q000473:pathology; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage; D000077143:Docetaxel; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D015996:Survival Rate; D043823:Taxoids / Q000008:administration & dosage; D016896:Treatment Outcome
D043823:Taxoids; D000077143:Docetaxel; D004317:Doxorubicin; D002945:Cisplatin