Purpose: To investigate the safety and pharmacokinetics of aerosolized Sustained Release Lipid

7131 Background: Investigate the safety and pharmacokinetics of aerosolized SLIT (Sustained release Lipid Inhalation Targeting) cisplatin in patients with carcinoma of the lung. Methods: In this single-center, dose-escalating study patients received SLIT cisplatin for a maximum of 6 cycles. The dose level defines the cycle duration and number of inhalations per day. Safety data, including laboratory parameters, adverse events, pulmonary function tests, bronchial responsiveness, and radiographic imaging were collected and analyzed for all patients in order to determine toxicity. Pharmacokinetic data was collected during the first treatment course. Results: 17 patients and 1 patient on compassionate use received treatment. SLIT cisplatin was well tolerated. No dose limiting toxicity was observed. The maximum delivered dose was 60 mg/m2 in a 2 week schedule and 40 mg/m2 on a weekly schedule. Safety data showed no hematological toxicity, nephrotoxicity, ototoxicity, or neurotoxicity. Common side effects were nausea (66.7%), vomiting (44.4%), dyspnea (66.7%), hoarseness (27.8%), and fatigue (66.7%). Pharmacokinetic data showed very low systemic concentrations only at the higher doses. CTC grade-2 decrease in FEV1 and DLCO occurred both in 2 patients after 1 course, and grade-1 decrease in FEV1 and DLCO in 6 and 4 patients respectively. Best overall response was stable disease in 13 patients, while 4 had progressive disease (1 patient received only one course). These results indicate that high doses of aerosolized SLIT cisplatin can be inhaled safely. The therapeutic effect of the formulation will be tested in a phase II study. Conclusions: Inhaled SLIT cisplatin was found to be feasible and safe in patients with lung cancer. [Table: see text]

The aim of this study was to determine the efficacy of using a high-efficiency particulate air (HEPA) filter air cleaning system, a demistifier, to reduce the potential risk of fugitive aerosol contact in health care personnel working with patients inhaling nebulized liposomal encapsulated SLIT (Sustained-release Lipid Inhalation Targeting) Cisplatin. Filters were used to sample platinum in the air outside the tent and from the tent's exhaust stream. Air collection was performed under three conditions: (1) during patient dosing (14 h of air collection); (2) immediately after the patient has left the demistifier tent (4 h of air collection); and (3) when 7 mL of drug product was nebulized to dryness in the tent without a patient being present. Filters were collected, and placed in an extraction solvent. Subsequently, the solvent was assayed for platinum content by inductively coupled plasma-mass spectrometry (ICP-MS). Platinum levels in the extraction solvent were indistinguishable from the blank controls for all conditions. Measured levels were below workplace exposure limits established for cisplatin by the Occupational Safety and Health Administration (i.e., 2 ng . (L(1)). In addition, the demistifier was able to effectively capture aerosolized SLIT Cisplatin following nebulization of 7 mL of drug product to dryness in the tent. The demistifier tent is effective at containing any nebulized liposomal encapsulated cisplatin during patient treatment. Importantly, because the tent's HEPA filtration system is effective at removing any nebulized liposomal cisplatin, the exhausted air, which is free of platinum, can be returned into the room with no additional ventilation precautions.

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