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Irinophore C: A liposome formulation of irinotecan with substantially improved therapeutic efficacy against a panel of human zenograft tumors

Citation

Ramsay, EC and Anantha, N and Zastre, J and Meijs, M and Zonderhuis, J and Strutt, D and Webb, MS and Waterhouse, D and Bally, MB, Irinophore C: A liposome formulation of irinotecan with substantially improved therapeutic efficacy against a panel of human zenograft tumors, Clinical Cancer Research, 15, (14) pp. 1208-1217. ISSN 1078-0432 (2008) [Refereed Article]


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Copyright Statement

Copyright 2008 American Association for Cancer Research

Official URL: http://clincancerres.aacrjournals.org/content/14/4...

DOI: doi:10.1158/1078-0432.CCR-07-0780

Abstract

Purpose: To assess the pharmacokinetics, tumor drug accumulation, and therapeutic activity of Irinophore C, a novel liposomal formulation of irinotecan (CPT-11). Experimental Design: The plasma lactone/carboxy levels of CPT-11 and SN-38 were determined in mice after a single i.v. dose of irinotecan (Camptosar), or Irinophore C, and the plasma t1/2, plasma area under the curve, plasma Cmax, and plasma clearance were calculated. Further, plasma and tumor drug levels were also measured in tumor-bearing mice following Irinophore C treatment. The efficacy of Irinophore C was compared with that of Camptosar in five s.c. human tumor xenografts using single-dose treatment (LS 180), a total of three doses administered at 4-day intervals (H460), or a total of three doses administered at 7-day intervals (Capan-1, PC-3, and HT-29). Results: Compared with Camptosar, Irinophore C mediated an 8-fold increase in t1/2, a 100-fold increase in Cmax, a 1,000-fold increase in area under the curve, and a 1,000-fold decrease in clearance for the active lactone form of CPT-11. Further, the plasma and tumor SN-38 lactone levels were consistent for at least 48 h post-Irinophore C injection. Camptosar treatment (40 mg/kg) mediated a delay in the time required for tumors to increase to four times their pretreatment size compared with controls (T-C). T-Cs ranged from 2 days (LS 180 model) to 18 days (PC-3 model). Irinophore C (40 mg/kg) engendered T-Cs ranging from 14 days (LS 180 model) to 87 days (Capan-1 model). Conclusion: Irinophore C improved CPT-11/SN-38 pharmacokinetics, promoted tumor drug accumulation, and increased therapeutic efficacy in a panel of five distinct human tumor xenografts.

Item Details

Item Type:Refereed Article
Keywords:liposome irinotecan CPT-11 SN-38 cancer xenografts
Research Division:Medical and Health Sciences
Research Group:Pharmacology and Pharmaceutical Sciences
Research Field:Clinical Pharmacology and Therapeutics
Objective Division:Health
Objective Group:Other Health
Objective Field:Health not elsewhere classified
Author:Ramsay, EC (Dr Euan Ramsay)
ID Code:51013
Year Published:2008
Web of Science® Times Cited:26
Deposited By:Pharmacy
Deposited On:2008-06-02
Last Modified:2011-06-03
Downloads:0

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