
<b>"A major factor in the failure of IV chemotherapy is the blood-brain barrier (BBB), a physiologic impediment to the delivery of cytotoxic chemotherapeutic drugs to the central nervous system (CNS). " [2]</b>

"Intra-arterial and intrathecal infusion, blood-brain barrier disruption, high-dose chemotherapy, intratumoral administration, and convection-enhanced delivery are methods developed to overcome the BBB.  Although some of these methods may increase the local concentration-time profile, improvement in clinical outcomes has yet to be definitively established. New methods for assessment of drug delivery to the brain tumor will assume increasing importance in the study of new cytotoxic chemotherapeutic drugs for these types of cancer. Pharmacokinetic studies are critical components of these clinical trials and allow assessment of drug delivery to the CNS and brain tumor. Additionally, pharmacokinetic studies will remain an important component of early clinical trials, particularly for identifying significant drug interactions involving the various supporting medications that are typically used in this patient population." [2]

"Therapeutic options for the treatment of malignant brain tumors have been limited, in part, because of the presence of the blood-brain barrier. For this reason, the Sixth Annual Meeting of the Blood-Brain Barrier Disruption Consortium,,,, was convened in April 2000. ,,, It brought together clinicians and basic scientists from across the U.S. to discuss the role of dose intensity and enhanced chemotherapy delivery in the treatment of malignant brain tumors and to design multicenter clinical trials. " [1]

"Optimizing chemotherapy delivery to the CNS is crucial. ,,,   The discovery that specific constellations of genetic alterations can predict which tumors are chemoresponsive, and can therefore more accurately predict prognosis, has important implications for delivery of intensive, effective chemotherapy regimens with acceptable toxicities. "  [1]

Efforts are also being made to create "cytoenhancers and chemoprotectants as part of dose-intensive regimens for chemosensitive brain tumors and development of improved gene therapies."  [1]
 
[1] Doolittle ND, Anderson CP, et.al.  Neuro-oncol 2001 Jan;3(1):46-54 
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[2]Ciordia R, Supko J, Gatineau M, Batchelor T.  Curr Oncol Rep 2000 Sep;2(5):445-53 
&&url PMID: 11122877

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<b>Temozolomide [Temodar] is a chemotherapy agent sometimes useful in LMS, which also crosses the blood brain barrier, and can sometimes create a response in a sensitive tumor.

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