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Tissue concentration of systemically administered antineoplastic agents in human brain tumors
Marshall W Pitz1, Arati Desai, Stuart A Grossman
1University of Manitoba, 675 McDermot Avenue, Winnipeg, MB, R3E 0V9, Canada. pitz@cc.umanitoba.ca
Abstract:
The blood-brain-barrier (BBB) limits the penetration of many systemic antineoplastic therapies. Consequently, many agents may be used in clinical studies and clinical practice though they may not achieve therapeutic levels within the tumor. We sought to compile the currently available human data on antineoplastic drug concentrations in brain and tumor tissue according to BBB status. A review of the literature was conducted for human studies providing concentrations of antineoplastic agents in blood and metastatic brain tumors or high-grade gliomas. Studies were considered optimal if they reported simultaneous tissue and blood concentration, multiple sampling times and locations, MRI localization, BBB status at sampling site, tumor histology, and individual subject data. Twenty-Four studies of 19 compounds were included. These examined 18 agents in contrast-enhancing regions of high-grade gliomas, with optimal data for 2. For metastatic brain tumors, adequate data was found for 9 agents. Considerable heterogeneity was found in the measurement value, tumor type, measurement timing, and sampling location within and among studies, limiting the applicability of the results. Tissue to blood ratios ranged from 0.054 for carboplatin to 34 for mitoxantrone in high-grade gliomas, and were lowest for temozolomide (0.118) and etoposide (0.116), and highest for mitoxantrone (32.02) in metastatic tumors. The available data examining the concentration of antineoplastic agents in brain and tumor tissue is sparse and limited by considerable heterogeneity. More studies with careful quantification of antineoplastic agents in brain and tumor tissue is required for the rational development of therapeutic regimens.
Insights
The blood-brain barrier (BBB) restricts anticancer drug delivery to brain tumors. Limited human data shows significant variability in drug concentrations, hindering effective treatment development for brain cancers.
Area of Science:
- Neuro-oncology
- Pharmacology
- Clinical Trials
Background:
- The blood-brain barrier (BBB) impedes systemic anticancer drug penetration into brain tumors.
- Many antineoplastic agents fail to reach therapeutic concentrations within the tumor site.
- This limits the efficacy of systemic therapies for brain malignancies.
Purpose of the Study:
- To compile and analyze human data on antineoplastic drug concentrations in brain and tumor tissue.
- To evaluate drug penetration relative to the blood-brain barrier (BBB) status.
- To identify data gaps and heterogeneity in existing research.
Main Methods:
- Systematic literature review of human studies reporting antineoplastic agent concentrations in blood and brain tumors (high-grade gliomas and metastases).
- Inclusion criteria focused on studies with simultaneous tissue/blood concentrations, multiple sampling times, MRI localization, BBB status, histology, and individual data.
- Data extraction and analysis of tissue-to-blood ratios for various antineoplastic agents.
Main Results:
- Twenty-four studies involving 19 compounds were included, with optimal data for only two agents in high-grade gliomas and nine in metastatic tumors.
- Significant heterogeneity was observed in measurement values, tumor types, timing, and sampling locations.
- Tissue-to-blood ratios varied widely, from 0.054 (carboplatin) to 34 (mitoxantrone) in high-grade gliomas, and 0.116 (etoposide) to 32.02 (mitoxantrone) in metastatic tumors.
Conclusions:
- Available human data on antineoplastic drug concentrations in brain tumors is sparse and highly heterogeneous.
- This variability limits the rational development of effective therapeutic regimens for brain cancers.
- Further studies with rigorous quantification are essential to optimize anticancer drug delivery across the BBB.
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