High dose weekly erlotinib achieves therapeutic concentrations in CSF and is effective in leptomeningeal metastases from epidermal growth factor receptor mutant lung cancer
Open accessAbstract
Leptomeningeal metastases (LM) occur in 5-10% of patients with solid tumors and are associated with a dismal prognosis. We describe LM from lung adenocarcinoma harboring a mutation in the epidermal growth factor receptor (EGFR) gene that confers sensitivity to the EGFR tyrosine kinase inhibitors (EGFR-TKIs) erlotinib and gefitinib. The CSF concentration of EGFR-TKIs achieved by standard daily dosing may be insufficient for therapeutic effect. However, intermittent (pulsatile) high dose administration (1000-1500 mg/week) achieves a higher CSF concentration than standard dosing, and successfully controlled LM in this patient.
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High-dose or pulsatile dosing of EGFR TKIs may produce a higher response rate in leptomeningeal disease.
“In particular, a high dose or pulsatile dosing may produce a higher response rate in this situation.[119][120][121]”
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- Authors
- Clarke, J. L., Pao, W., Wu, N., Miller, V. A., & Lassman, A. B.
- Affiliations
- Memorial Sloan Kettering Cancer Center (US)
- Corresponding author
- Lassman, Andrew B.
- Venue
- Journal of Neuro-Oncology
- Published
- 2010-02-10
- Volume
- 99
- Issue
- 2
- Pages
- 283-286
- ISSN
- 0167-594X (ISSN-L)
- 1573-7373
- PMC
- PMC3973736
- OpenAlex
- W2060254075
- Cited by
- 214
- References
- 9
- Citations by year
- 2026: 4 · 2024: 7 · 2023: 8 · 2022: 5 · 2021: 7 · 2020: 13 · 2019: 9 · 2018: 15 · 2017: 25 · 2016: 25 · 2015: 21 · 2014: 18 · 2013: 20 · 2012: 19
- FWCI
- 14.94
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Journal of Neuro-Oncology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Cancer Institute (R01CA121210)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Brain Metastases and Treatment
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
- Health Sciences › Medicine › Genetics › Glioma Diagnosis and Treatment
- Keywords
- leptomeningeal metastasis, erlotinib, EGFR tyrosine kinase inhibitors, EGFR mutation, lung adenocarcinoma, cerebrospinal fluid drug concentration, gefitinib, brain metastasis treatment
- MeSH terms
- Erlotinib Hydrochloride, Adenocarcinoma, Female, Humans, Lung Neoplasms, Male, Meningeal Neoplasms, Middle Aged, Mutation, Quinazolines, Treatment Outcome, Protein Kinase Inhibitors, ErbB Receptors
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