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This Article Full Text Full Text (PDF) All Versions of this Article: 9/1/20    most recent 15228517-2006-016v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (3) Citing Articles via Google Scholar Google Scholar Articles by Yamashita, Y. Articles by Bankiewicz, K. S. Search for Related Content PubMed PubMed Citation

Convection-enhanced delivery of a topoisomerase I inhibitor (nanoliposomal topotecan) and a topoisomerase II inhibitor (pegylated liposomal doxorubicin) in intracranial brain tumor xenografts¹

Department of Neurological Surgery, Brain Tumor Research Center (Y.Y., M.T.K., T.K., K.S.B.), and Division of Hematology-Oncology (C.O.N., J.W.P.), University of California, San Francisco, San Francisco, CA 94103; and Hermes Biosciences, Inc., South San Francisco, CA 94080 (D.C.D., J.W.P.); USA

³ Address correspondence to Krystof S. Bankiewicz, Department of neurological Surgery, University of California, San Francisco, 1855 Folsom Street, Mission Center Building room 226, San Francisco, CA 94103, USA (Krystof.Bankiewicz{at}ucsf.edu).

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.

Key Words: brain tumor • CED • convection-enhanced delivery • glioma • liposome • topotecan

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				M. T. Krauze, C. O. Noble, T. Kawaguchi, D. Drummond, D. B. Kirpotin, Y. Yamashita, E. Kullberg, J. Forsayeth, J. W. Park, and K. S. Bankiewicz Convection-enhanced delivery of nanoliposomal CPT-11 (irinotecan) and PEGylated liposomal doxorubicin (Doxil) in rodent intracranial brain tumor xenografts Neuro-oncol, October 1, 2007; 9(4): 393 - 403. [Abstract] [Full Text] [PDF]