Convection enhanced delivery for treating brain tumors and selected neurological disorders: symposium review

Vogelbaum, Michael A.

doi:10.1007/s11060-006-9308-9

Cited by 68 publications

(41 citation statements)

References 25 publications

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“…Median survival was comparable between the two groups and hence the study failed to meet its goal of improving survival of more than 50%. 47,48 A phase I study of CED of IL13-PE38QQR followed by radiation therapy with and without temozolomide in newly diagnosed malignant glioma revealed a well-tolerated therapy in these patients. 49 …”

Section: Il-4 and Il-13 Targeted Toxinsmentioning

confidence: 99%

Novel Drug Delivery Strategies in Neuro-Oncology

2009

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Summary: Treatment of malignant gliomas represents one of the most formidable challenges in oncology. Despite treatment with surgery, radiation therapy, and chemotherapy, the prognosis remains poor, particularly for glioblastoma, which has a median survival of 12 to 15 months. An important impediment to finding effective treatments for malignant gliomas is the presence of the blood brain barrier, which serves to prevent delivery of potentially active therapeutic compounds. Multiple efforts are focused on developing strategies to effectively deliver active drugs to brain tumor cells. Blood brain barrier disruption and convectionenhanced delivery have emerged as leading investigational delivery techniques for the treatment of malignant brain tumors. Clinical trials using these methods have been completed, with mixed results, and several more are being initiated. In this review, we describe the clinically available methods used to circumvent the blood brain barrier and summarize the results to date of ongoing and completed clinical trials. Key Words: Convection-enhanced delivery, blood brain barrier disruption, brain neoplasm, drug delivery system.

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Section: Il-4 and Il-13 Targeted Toxinsmentioning

confidence: 99%

Novel Drug Delivery Strategies in Neuro-Oncology

2009

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“…The CED technique involves the pressurized infusion of therapeutic agents directly into tumor other target tissues using specialized catheters (13,(62)(63)(64). By bypassing the BBB, CED allows for delivery of high concentrations of macromolecular drugs directly to the tumor with negligible or no systemic drug exposure, and CED is capable of achieving clinically relevant drug distribution volumes by bulk fluid flow without significantly increasing intracranial pressure when infusions are administered at low pressures over several hours or days (60,(62)(63)(64).…”

Section: Convection-enhanced Deliverymentioning

confidence: 99%

“…By bypassing the BBB, CED allows for delivery of high concentrations of macromolecular drugs directly to the tumor with negligible or no systemic drug exposure, and CED is capable of achieving clinically relevant drug distribution volumes by bulk fluid flow without significantly increasing intracranial pressure when infusions are administered at low pressures over several hours or days (60,(62)(63)(64). CED can increase drug distribution volumes in the brain by at least an order of magnitude relative to simple diffusion, and it can be performed safely throughout the CNS in humans and animals (65).…”

Section: Convection-enhanced Deliverymentioning

confidence: 99%

Maximizing Local Access to Therapeutic Deliveries in Glioblastoma. Part V: Clinically Relevant Model for Testing New Therapeutic Approaches

Rossmeisl

2017

Glioblastoma

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A significant obstacle to the development of new brain tumor therapeutics remains the lack of rodent models that faithfully reproduce the in vivo complexities of human glioblastoma. Dogs and humans are the only species that frequently develop spontaneous brain tumors. Remarkable clinical, phenotypic, and molecular similarities exist between human and canine malignant glioma. Our research has focused on the development of pharmacologically tractable molecular targets common to human and canine gliomas, as well as the discovery Canine Brain Tumor Models 406 and refinement of novel methods of drug delivery to the brain, such as convection-enhanced delivery (CED), irreversible electroporation (IRE), and focused ultrasound, that can overcome the limitations imposed by the bloodbrain and blood-tumor barriers. Through the conduct of early phase clinical trials in dogs, we demonstrate the safety, feasibility, and preliminary efficacies of IL-13RA2-and EphA2-targeted bacterial cytotoxins and IRE for the treatment of spontaneous malignant glioma, illustrate the clinical utility of real-time imaging monitored CED as a robust drug delivery platform, and describe the use of the tumor-bearing dog in transcranial-focused ultrasound applications related to neuro-oncology. The dog brain cancer model offers unique opportunities to expedite the clinical translation of cancer therapeutics through the design of preclinical investigations that ask and answer drug and medical device development questions that cannot be sufficiently addressed in rodent models.

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“…The infusion establishes a pressure gradient that induces a flow in the brain away from the needle. Small molecules can be delivered over relatively large distances in the brain, but larger molecules, including certain proteins with proven efficacy against malignant cells, are hindered in their transport (Bobo et al, 1994 andVogelbaum, 2007). As a result, they cannot travel sufficiently far to reach migratory malignant cells.…”

Section: Introductionmentioning

confidence: 99%