期刊
NEURO-ONCOLOGY
卷 9, 期 1, 页码 20-28出版社
DUKE UNIV PRESS
DOI: 10.1215/15228517-2006-016
关键词
brain tumor; CED; convection-enhanced delivery; glioma; liposome; topotecan
资金
- NCI NIH HHS [U54 CA090788, U54 CA90788, N01-CO-27031-16] Funding Source: Medline
- NATIONAL CANCER INSTITUTE [U54CA090788] Funding Source: NIH RePORTER
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 single-agent 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.
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