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

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

Research output: Contribution to journalArticle

266 Citations (Scopus)

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

Fingerprint

Brain Neoplasms
Central Nervous System
Drug Therapy
Neoplasms
Cerebrospinal Fluid
Blood-Brain Barrier
Choroid Plexus
Clinical Pharmacology
Therapeutics
Glioblastoma
Pharmaceutical Preparations
Lymphoma
Pharmacology
Neoplasm Metastasis
Brain

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

Cite this

Chemotherapy delivery issues in central nervous system malignancy : A reality check. / Muldoon, Leslie; Soussain, Carole; Jahnke, Kristoph; Johanson, Conrad; Siegal, Tali; Smith, Quentin R.; Hall, Walter A.; Hynynen, Kullervo; Senter, Peter D.; Peereboom, David M.; Neuwelt, Edward.

In: Journal of Clinical Oncology, Vol. 25, No. 16, 01.06.2007, p. 2295-2305.

Research output: Contribution to journalArticle

Muldoon, L, Soussain, C, Jahnke, K, Johanson, C, Siegal, T, Smith, QR, Hall, WA, Hynynen, K, Senter, PD, Peereboom, DM & Neuwelt, E 2007, 'Chemotherapy delivery issues in central nervous system malignancy: A reality check', Journal of Clinical Oncology, vol. 25, no. 16, pp. 2295-2305. https://doi.org/10.1200/JCO.2006.09.9861
Muldoon, Leslie ; Soussain, Carole ; Jahnke, Kristoph ; Johanson, Conrad ; Siegal, Tali ; Smith, Quentin R. ; Hall, Walter A. ; Hynynen, Kullervo ; Senter, Peter D. ; Peereboom, David M. ; Neuwelt, Edward. / Chemotherapy delivery issues in central nervous system malignancy : A reality check. In: Journal of Clinical Oncology. 2007 ; Vol. 25, No. 16. pp. 2295-2305.
@article{ec2a73afc2ed42cfb2f582f536c7dbe4,
title = "Chemotherapy delivery issues in central nervous system malignancy: A reality check",
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.",
author = "Leslie Muldoon and Carole Soussain and Kristoph Jahnke and Conrad Johanson and Tali Siegal and Smith, {Quentin R.} and Hall, {Walter A.} and Kullervo Hynynen and Senter, {Peter D.} and Peereboom, {David M.} and Edward Neuwelt",
year = "2007",
month = "6",
day = "1",
doi = "10.1200/JCO.2006.09.9861",
language = "English (US)",
volume = "25",
pages = "2295--2305",
journal = "Journal of Clinical Oncology",
issn = "0732-183X",
publisher = "American Society of Clinical Oncology",
number = "16",

}

TY - JOUR

T1 - Chemotherapy delivery issues in central nervous system malignancy

T2 - A reality check

AU - Muldoon, Leslie

AU - Soussain, Carole

AU - Jahnke, Kristoph

AU - Johanson, Conrad

AU - Siegal, Tali

AU - Smith, Quentin R.

AU - Hall, Walter A.

AU - Hynynen, Kullervo

AU - Senter, Peter D.

AU - Peereboom, David M.

AU - Neuwelt, Edward

PY - 2007/6/1

Y1 - 2007/6/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=34250182404&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34250182404&partnerID=8YFLogxK

U2 - 10.1200/JCO.2006.09.9861

DO - 10.1200/JCO.2006.09.9861

M3 - Article

C2 - 17538176

AN - SCOPUS:34250182404

VL - 25

SP - 2295

EP - 2305

JO - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

SN - 0732-183X

IS - 16

ER -