The technology of local delivery is being utilized to target multiple pathways for brain tumor therapy. Through the combination
of Gliadel, radiation therapy and oral temozolomide (TMZ), median patient survival has increased from 9 to 21 months.
To further increase survival, we are exploring the local delivery of TMZ and have shown that in animal models we can achieve
37.5% long term survival. This benefit dramatically increases when combined with radiation therapy. We have also incorporated
paclitaxel, a mitotic inhibitor, into a thermosensitive gel depot which provides local delivery, enhances efficacy, and limits systemic
toxicity. In combination with TMZ and radiation therapy, this depot significantly increases the long term survivors and improves
median survival compared to either therapy alone. This data led to a Phase I clinical trial. Rapamycin, an MTOR inhibitor, anti-
angiogenic agent, and anti-proliferative agent has been efficiently incorporated and delivered using biodegradable, controlled
release beads which are safe for CNS delivery. These locally delivered beads prolonged survival in the 9L rodent glioma model.
Microchip direct delivery to the brain is increasingly attractive. Intracranial microdialysis has determined that the intratumoral
concentration of temozolomide was not adversely effected after systemic Avastin dosing, showing that this combination may be
helpful to brain tumor patients. This technique is aiding in our assessment of the interaction between the BBB and compounds
given both systemically and locally.
Betty Tyler is an Assistant Professor of Neurosurgery at Johns Hopkins University. She runs a highly successful and productive laboratory and has a
national reputation for stellar science in the field of translational research and local delivery of chemotherapeutic agents for brain tumor therapy. She
assisted in the preclinical studies that led to bringing of Gliadel to brain tumor patients as a standard of care, and currently the focus of Betty?s work
and primary funding has been to develop and take other locally delivered chemotherapeutic agent to clinical trials.
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