Chemotherapy delivery issues in central nervous system malignancy: A reality check

Leslie L. Muldoon, Carole Soussain, Kristoph Jahnke, Conrad Johanson, Tali Siegal, Quentin R. Smith, Walter A. Hall, Kullervo Hynynen, Peter D. Senter, David M. Peereboom, Edward A. Neuwelt

Research output: Contribution to journalReview article

277 Scopus citations

Abstract

Purpose: This review assesses the current state of knowledge regarding preclinical and clinical pharmacology for brain tumor chemotherapy and evaluates relevant brain tumor pharmacology studies before October 2006. Results: Chemotherapeutic regimens in brain tumor therapy have often emerged from empirical clinical studies with retrospective pharmacologic explanations, rather than prospective trials of rational chemotherapeutic approaches. Brain tumors are largely composed of CNS metastases of systemic cancers. Primary brain tumors, such as glioblastoma multiforme or primary CNS lymphomas, are less common. Few of these tumors have well-defined optimal treatment. Brain tumors are protected from systemic chemotherapy by the blood-brain barrier (BBB) and by intrinsic properties of the tumors. Pharmacologic studies of delivery of conventional chemotherapeutics and novel therapeutics showing actual tumor concentrations and biologic effect are lacking. Conclusion: In this article, we review drug delivery across the BBB, as well as blood-tumor and -cerebrospinal fluid (CSF) barriers, and mechanisms to increase drug delivery to CNS and CSF tumors. Because of the difficulty in treating CNS tumors, innovative treatments and alternative delivery techniques involving brain/cord capillaries, choroid plexus, and CSF are needed.

Original languageEnglish (US)
Pages (from-to)2295-2305
Number of pages11
JournalJournal of Clinical Oncology
Volume25
Issue number16
DOIs
StatePublished - Jun 1 2007

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Muldoon, L. L., Soussain, C., Jahnke, K., Johanson, C., Siegal, T., Smith, Q. R., Hall, W. A., Hynynen, K., Senter, P. D., Peereboom, D. M., & Neuwelt, E. A. (2007). Chemotherapy delivery issues in central nervous system malignancy: A reality check. Journal of Clinical Oncology, 25(16), 2295-2305. https://doi.org/10.1200/JCO.2006.09.9861