Phase I study of aerosolized SLIT cisplatin in the treatment of patients with carcinoma of the lung.
OBJECTIVE
To investigate the safety and pharmacokinetics of aerosolized Sustained Release Lipid Inhalation Targeting (SLIT) Cisplatin in patients with lung carcinoma.


METHODS
Phase I, dose-escalating study of SLIT Cisplatin given in two sessions daily. Safety data, including laboratory variables, adverse events, pulmonary function tests, and radiographic imaging, were collected and analyzed for all patients to determine toxicity. Pharmacokinetic monitoring was done during the first course.


RESULTS
Seventeen patients and one tracheostomy patient on compassionate use received treatment. Aerosolized cisplatin was well tolerated. No dose-limiting toxicity was observed at the maximum delivered dose. Safety data showed no hematologic toxicity, nephrotoxicity, ototoxicity, or neurotoxicity. Most common adverse events were nausea (64.7%), vomiting (47.1%), dyspnea (64.7%), fatigue (64.7%), and hoarseness (47.1%). Pharmacokinetic data showed very low plasma platinum levels only with the longest repeated inhalations. Common Toxicity Criteria grade 2 decrease in forced expiratory volume in one second and diffusing lung capacity for carbon monoxide after one course occurred both in two patients and grade one decrease in forced expiratory volume in one second and diffusing lung capacity for carbon monoxide in six and five patients, respectively. Direct airway deposition via the tracheostomy resulted in clinical deterioration after two cycles best described as bronchitis, completely reversible within days. Overall response: stable disease in 12 patients and progressive disease in 4 patients (one patient received one cycle).


CONCLUSIONS
Aerosolized liposomal cisplatin was found to be feasible and safe.
Wittgen
Bart P H
BP
Department of Pulmonary Diseases, VU University Medical Center, Amsterdam, the Netherlands.
Kunst
Peter W A
PW
van der Born
Kasper
K
van Wijk
Atie W
AW
Perkins
Walter
W
Pilkiewicz
Frank G
FG
Perez-Soler
Roman
R
Nicholson
Susan
S
Peters
Godefridus J
GJ
Postmus
Pieter E
PE
D000280:Administration, Inhalation; D000328:Adult; D000336:Aerosols; D000368:Aged; D000970:Antineoplastic Agents / Q000633:toxicity; D002945:Cisplatin / Q000008:administration & dosage / Q000633:toxicity*; D003692:Delayed-Action Preparations; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D008875:Middle Aged; D012449:Safety
D000336:Aerosols; D000970:Antineoplastic Agents; D003692:Delayed-Action Preparations; D002945:Cisplatin