Cisplatin is one of the most commonly used chemotherapy in lung cancer despite its high nephrotoxicity leading to an administration only every 3-4 weeks. This study is the first report of a preclinical investigation of therapeutic intensification combining a cisplatin dry powder for inhalation (CIS-DPI) with an intravenous (iv) cisplatin-based treatment. CIS-DPI with 50% cisplatin content (CIS-DPI-50) was developed using lipid excipients through scalable processes (high-speed and high-pressure homogenization and spray-drying). CIS-DPI-50 showed good aerodynamic performance (fine particle fraction of ~ 55% and a mass median aerodynamic particle size of ~ 2 µm) and a seven-fold increase and decrease in Cmax in the lungs and in plasma, respectively, in comparison with an iv cisplatin solution (CIS-iv) in healthy mice. Finally, the addition of CIS-DPI-50 to the standard cisplatin/paclitaxel iv doublet increased the response rate (67% vs 50%), decreased the tumour growth and prolonged the median survival (31 vs 21 days), compared to the iv doublet in the M109 lung carcinoma model tending to demonstrate a therapeutic intensification of cisplatin.
Keywords: Chemotherapy; Combination; Controlled-release; Lung retention; Non-small cell lung cancer; Pulmonary delivery.
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