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Cytotoxic chemotherapy: Advances in delivery, pharmacology, and testing

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Abstract

Adjuvant treatment of malignant gliomas, the most common types of primary brain tumors, with intravenous (iv) chemotherapy has not significantly improved survival for patients with these forms of cancer. 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). 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 indentifying significant drug interactions involving the various supporting medications that are typically used in this patient population.

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Authors and Affiliations

  1. Brain Tumor Center, Massachusetts General Hospital Cancer Center, Harvard Medical School, Cox 315, 100 Blossom Street, 02114, Boston, MA, USA

    Roberto Ciordia MD & Tracy Batchelor MD

  2. Division of Hematology/Oncology, Massachusetts General Hospital Cancer Center, Harvard Medical School, Cox 315, 100 Blossom Street, 02114, Boston, MA, USA

    Jeffrey Supko PhD & Michel Gatineau MD

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  3. Michel Gatineau MD
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Ciordia, R., Supko, J., Gatineau, M. et al. Cytotoxic chemotherapy: Advances in delivery, pharmacology, and testing. Curr Oncol Rep 2, 445–453 (2000). https://doi.org/10.1007/s11912-000-0065-1

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