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.
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Authors | Yoji Yamashita, Michal T Krauze, Tomohiro Kawaguchi, Charles O Noble, Daryl C Drummond, John W Park, Krystof S Bankiewicz |
Journal | Neuro-oncology
(Neuro Oncol)
Vol. 9
Issue 1
Pg. 20-8
(Jan 2007)
ISSN: 1522-8517 [Print] England |
PMID | 17018695
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antineoplastic Agents
- Topoisomerase I Inhibitors
- Topoisomerase II Inhibitors
- liposomal doxorubicin
- Polyethylene Glycols
- Topotecan
- Doxorubicin
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Topics |
- 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
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