Chemotherapy delivery issues in central nervous system malignancy: a reality check.
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.
Muldoon
Leslie L
LL
Department of Neurology, Oregon Health and Science University, Portland, and the Veterans Administration Medical Center, OR 97239-3098, USA.
Soussain
Carole
C
Jahnke
Kristoph
K
Johanson
Conrad
C
Siegal
Tali
T
Smith
Quentin R
QR
Hall
Walter A
WA
Hynynen
Kullervo
K
Senter
Peter D
PD
Peereboom
David M
DM
Neuwelt
Edward A
EA
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
D000970:Antineoplastic Agents