Early cessation of the clinical development of LiPlaCis, a liposomal cisplatin formulation

Purpose To evaluate the safety and tolerability of LiPlaCis a liposomal formulated platinum compound in patients with solid tumours and to determine the maximum tolerated dose (MTD) of intravenous v) LiPlaCis and to assess plasma and urine pharmacokinetics and plasma biomarkers Patients and methods Patients with solid tumours without standard therapeutic options were enrolled to receive LiPlaCis administered as a 1 h infusion without additional hydration every 3 weeks until RECIST progression or unacceptable toxicity Cohorts of 3-6 patients were treated at each dose level until MTD was reached Results Eighteen patients were enrolled and 64 cycles were delivered At the first dose level 3 patients experienced an infusion reaction Despite prophylactic pre medication and prolongation of the infusion to 2 h in further patients three other patients had mild acute infusion reactions Toxicity at the fifth dose level of 120 mg consisted of grade 2 renal toxicity reversible after hydration in 2 patients and grade 4 thrombocytopaenia in one of these patients Peak plasma concentrations and AUC were dose proportional The interpatient variability in the clearance of total LiPlaCis derived platinum was 41% Platinum was excreted via the urine mainly during the first 24 h after administration Investigated plasma biomarkers sPLA(2) and SC5b 9 were related to but not predictive for acute infusion reactions Conclusion The observed safety profile suggests no benefit over standard cisplatin formulations and LiPlaCis will require reformulation to enable further development (C) 2010 Elsevier Ltd All rights reserved