Cancer Chemotherapy and Pharmacology

, Volume 30, Issue 4, pp 251–260

Do anticancer agents reach the tumor target in the human brain?

  • M. G. Donelli
  • M. Zucchetti
  • M. D'Incalci
Review Antitumoral Agents, Brain Pharmacokinetics, Central Nervous System, Human Tumors

DOI: 10.1007/BF00686291

Cite this article as:
Donelli, M.G., Zucchetti, M. & D'Incalci, M. Cancer Chemother. Pharmacol. (1992) 30: 251. doi:10.1007/BF00686291

Summary

The development of effective chemotherapy for tumors of the central nervous system (CNS) is complicated in that the blood-brain barrier (BBB) hampers the penetration of most drugs into the brain and cerebrospinal fluid (CSF). This review summarizes the main reports on the distribution to CNS tumors and peritumoral normal brain of antitumor agents such as epipodophyllotoxins,cis-diamminedichloroplatinum(II), some nitrosoureas, bleomycin, vinblastine, and other clinically used antitumor agents as well as that of some experimental compounds with specific physicochemical properties. Drug levels were measured at surgical resection or in autopsy samples taken from patients who presented with different primary brain tumors or with brain metastases from extracerebral tumors. The observations made in each study were summarized in some detail, and the main points were then evaluated comparatively so as to highlight common aspects in the pharmacokinetic patterns of antitumor agents in human CNS tumors. Independently of their physicochemical properties, most antitumor agents appear to accumulate to a greater extent and to persist longer in intracerebral tumors than in the normal peritumoral brain. From in vitro cytotoxicity assays, it appears that epipodophyllotoxins, platinum compounds, bleomycin, and nitrosoureas reach potentially active therapeutic concentrations at the tumor target. However, all drugs have difficulty in reaching brain tissue adjacent to the tumor, as the intact BBB hampers their penetration. Plasma and CSF drug concentrations usually give little useful indication of the absolute quantity of drugs in brain tumors. To obtain a clear understanding of the CNS distribution of antitumor agents, one must determine whether the compound being measured is actually responsible for the observed activity and must consider the role of metabolites in the effect of the parent drug.

Abbreviations

AZQ

aziridinylbenzoquinone

BBB

blood-brain barrier

CNS

central nervous system

CSF

cerebrospinal fluid

BCNU

carmustine

BLEO

bleomycin

CDDP

cisplatin

DAU

3-deazauridine

DBD

dibromodulcitol

DTIC

dimethyl triazene imidazole carboxamide

MGBG

methylglyoxal bis(guanylhydrazone)

MITXR

mitoxantrone

PALA

N-phosphonacetyl-l-aspartate

PMM

pentamethylmelamine

TCNU

tauromustine

VLB

vinblastine

VM-26

teniposide

VP-16

etoposide

Copyright information

© Springer-Verlag 1992

Authors and Affiliations

  • M. G. Donelli
    • 1
    • 2
  • M. Zucchetti
    • 1
  • M. D'Incalci
    • 1
  1. 1.Instituto di Ricerche Farmacologische Mario NegriMILANOItaly
  2. 2.Dipartimento di Biologia e Genetica per le Scienze MedicheMilanoItaly