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PMID: 17018695 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Convection-enhanced delivery of a topoisomerase I inhibitor (nanoliposomal topotecan) and a topoisomerase II inhibitor (pegylated liposomal doxorubicin) in intracranial brain tumor xenografts.

Neuro-oncology ·Vol. 9 ·No. 1 ·2007-01-00 ·Pages 20-8

Yamashita Y, Krauze MT, Kawaguchi T, Noble CO, Drummond DC, Park JW, Bankiewicz KS

Abstract

Despite multimodal treatment options, the response and survival rates for patients with malignant gliomas remain dismal. Clinical trials with convection-enhanced delivery (CED) have recently opened a new window in neuro-oncology to the direct delivery of chemotherapeutics to the CNS, circumventing the blood-brain barrier and reducing systemic side effects. Our previous CED studies with liposomal chemotherapeutics have shown promising antitumor activity in rodent brain tumor models. In this study, we evaluated a combination of nanoliposomal topotecan (nLs-TPT) and pegylated liposomal doxorubicin (PLD) to enhance efficacy in our brain tumor models, and to establish a CED treatment capable of improving survival from malignant brain tumors. Both liposomal drugs decreased key enzymes involved in tumor cell replication in vitro. Synergistic effects of nLs-TPT and PLD on U87MG cell death were found. The combination displayed excellent efficacy in a CED-based survival study 10 days after tumor cell implantation. Animals in the control group and those in singleagent groups had a median survival of less than 30 days, whereas the combination group experienced a median survival of more than 90 days. We conclude that CED of two liposomal chemotherapeutics (nLs-TPT and PLD) may be an effective treatment option for malignant gliomas.

MeSH Terms
Animals Antineoplastic Agents/administration & dosage Brain Neoplasms/drug therapy,pathology Cell Line, Tumor Doxorubicin/administration & dosage,analogs & derivatives Drug Delivery Systems Glioblastoma/drug therapy,pathology Humans Male Polyethylene Glycols/administration & dosage Rats Rats, Nude Rats, Sprague-Dawley Survival Rate Topoisomerase I Inhibitors Topoisomerase II Inhibitors Topotecan/administration & dosage Xenograft Model Antitumor Assays
Chemicals
Antineoplastic Agents Topoisomerase I Inhibitors Topoisomerase II Inhibitors liposomal doxorubicin Polyethylene Glycols Topotecan Doxorubicin
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Yamashita Yoji
Department of Neurological Surgery, Brain Tumor Research Center, University of California, San Francisco, San Francisco, CA 94103, USA.
Krauze Michal T
Kawaguchi Tomohiro
Noble Charles O
Drummond Daryl C
Park John W
Bankiewicz Krystof S
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Article Info
Journal
Neuro-oncology
Abbr.
Neuro Oncol
ISSN
1522-8517
DOI
10.1215/15228517-2006-016
Published
2007-01-00
Epub
2006-00-03
Pages
20-8
Language
English
Region
England
NLM ID
100887420
PMCID
PMC1828110
Subset
IM
Grants
NCI NIH HHS · U54 CA090788 · United States
NCI NIH HHS · N01-CO-27031-16 · United States
NCI NIH HHS · U54 CA90788 · United States
External Links
PubMed source DOI: 10.1215/15228517-2006-016 PMC Full Text View journal details
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