title: Chemotherapy delivery issues in central nervous system malignancy: a reality check.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Neurology, Oregon Health and Science University, Portland, and the Veterans Administration Medical Center, OR 97239-3098, USA.
authors.forename: Leslie L
authors.initials: LL
authors.lastname: Muldoon
authors.forename: Carole
authors.initials: C
authors.lastname: Soussain
authors.forename: Kristoph
authors.initials: K
authors.lastname: Jahnke
authors.forename: Conrad
authors.initials: C
authors.lastname: Johanson
authors.forename: Tali
authors.initials: T
authors.lastname: Siegal
authors.forename: Quentin R
authors.initials: QR
authors.lastname: Smith
authors.forename: Walter A
authors.initials: WA
authors.lastname: Hall
authors.forename: Kullervo
authors.initials: K
authors.lastname: Hynynen
authors.forename: Peter D
authors.initials: PD
authors.lastname: Senter
authors.forename: David M
authors.initials: DM
authors.lastname: Peereboom
authors.forename: Edward A
authors.initials: EA
authors.lastname: Neuwelt
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics*; D001812:Blood-Brain Barrier; D001921:Brain / Q000378:metabolism; D001932:Brain Neoplasms / Q000188:drug therapy*; D016503:Drug Delivery Systems; D006801:Humans
chemical_list: D000970:Antineoplastic Agents