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Do anticancer agents reach the tumor target in the human brain?
M G Donelli1, M Zucchetti, M D'Incalci
1Istituto di Ricerche Farmacologiche Mario Negri, Milano, Italy.
Cancer Chemotherapy and Pharmacology
|January 1, 1992
Summary
Chemotherapy for brain tumors is challenging due to the blood-brain barrier (BBB). While some drugs accumulate in tumors, penetration into surrounding brain tissue remains limited, complicating effective treatment.
Area of Science:
- Neuro-oncology
- Pharmacology
- Drug Delivery
Background:
- The blood-brain barrier (BBB) significantly impedes central nervous system (CNS) chemotherapy effectiveness.
- Understanding drug distribution within CNS tumors and surrounding brain tissue is crucial.
Purpose of the Study:
- To review and summarize existing reports on the distribution of various antitumor agents in CNS tumors and normal brain tissue.
- To identify common pharmacokinetic patterns of chemotherapy drugs in human CNS tumors.
Main Methods:
- Compilation and comparative evaluation of studies measuring drug levels in surgical or autopsy samples from patients with CNS tumors.
- Analysis of drug distribution data for clinically used and experimental antitumor agents.
Main Results:
- Most antitumor agents show greater accumulation and longer persistence in intracerebral tumors compared to normal peritumoral brain.
- Certain agents like epipodophyllotoxins, platinum compounds, bleomycin, and nitrosoureas may reach therapeutic concentrations within tumors.
- The intact BBB significantly limits drug penetration into brain tissue adjacent to tumors.
Conclusions:
- Drug levels in plasma and cerebrospinal fluid (CSF) offer limited insight into brain tumor drug concentrations.
- Accurate assessment of CNS drug distribution requires considering drug metabolites and their contribution to therapeutic activity.