Document Detail


Early cessation of the clinical development of LiPlaCis, a liposomal cisplatin formulation.
MedLine Citation:
PMID:  20801016     Owner:  NLM     Status:  In-Process    
Abstract/OtherAbstract:
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 (i.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 3weeks 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.
Authors:
Maja J A de Jonge; Marije Slingerland; Walter J Loos; Erik A C Wiemer; Herman Burger; Ron H J Mathijssen; Judith R Kroep; Margret A G den Hollander; Diane van der Biessen; Mei-Ho Lam; Jaap Verweij; Hans Gelderblom
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-08-26
Journal Detail:
Title:  European journal of cancer (Oxford, England : 1990)     Volume:  46     ISSN:  1879-0852     ISO Abbreviation:  Eur. J. Cancer     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-10-25     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9005373     Medline TA:  Eur J Cancer     Country:  England    
Other Details:
Languages:  eng     Pagination:  3016-21     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Elsevier Ltd. All rights reserved.
Affiliation:
Erasmus University Medical Center Daniel Den Hoed Cancer Center, Department of Medical Oncology, Rotterdam, The Netherlands. m.dejonge@erasmusmc.nl
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