One reason chemotherapy has not had as great an impact in the treatment of brain tumors as it has in other childhood cancers is because of the blood-brain barrier, which limits the penetration into the brain of most systemically administered anti-cancer. The approaches being taken to address this issue include (1) identifying agents that penetrate across the blood-brain barrier effectively, (2) determining if agents can modify the CNS penetration of standard chemotherapeutic drugs, (3) studying regional administration of anti-cancer agents and (4) exploring the use of differentiation agents for the treatment of neural tumors.

Currently we are investigating the use of selectively disrupting the blood-brain barrier with the bradykinin analog RMP-7. We are conducting a pediatric phase 2 trial of the combination of RMP-7/carboplatin in children with brain tumors. In addition to detailed pharmacokinetic studies, magnetic resonance spectroscopy is being performed to evaluate the acute effects of RMP-7/carboplatin on pediatric brain tumors. One approach being evaluated is with the use of differentiation agents. Currently phenylacetate and phenylbutyrate, which in vitro induces differentiation in a variety of glial cell lines, are being tested in a pediatric phase 1 and 2 trials. A trial of the PDGF-receptor pathway inhibitor SU101 is also underway.

Also See Brain Tumor Protocols

Last Updated: March 10, 2003

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