High-dose, pulsatile erlotinib in two NSCLC patients with leptomeningeal metastases—one with a remarkable thoracic response as well
Abstract
A considerable number of patients with epidermal growth factor receptor (EGFR)-mutated non-small-cell lung cancer (NSCLC) develop leptomeningeal metastases. Leptomeningeal metastases are associated with deterioration of clinical symptoms and poor survival. Traditionally, treatment of metastases in the central nervous system consists of radiotherapy and less frequently, surgery. The role of systemic therapy is limited due to the blood-brain barrier inhibiting pharmacological doses to be reached in the central nervous system. Several case reports have described high-dose, pulsatile tyrosine kinase inhibitors as an effective treatment of leptomeningeal metastases, based on the hypothesis that higher concentrations in the cerebrospinal fluid can be reached by higher systemic concentrations. Here, we describe two patients with EGFR-mutated non-small cell lung cancer, with both clinical and radiological response to this high-dose, pulsatile regimen. Interestingly, one patient showed a remarkable response of intrathoracic response as well.
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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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References 22 · Cited by 46
- Authors
- Kuiper, J. L., & Smit, E. F.
- Affiliations
- Amsterdam UMC Location Vrije Universiteit Amsterdam (NL)
- Corresponding author
- Kuiper, J.L.
- ORCID
- Smit, E.F.
- Venue
- Lung Cancer
- Publisher
- Elsevier BV
- Published
- 2013-04
- Volume
- 80
- Issue
- 1
- Pages
- 102-105
- ISSN
- 0169-5002 (ISSN-L)
- OpenAlex
- W2000154295
- Cited by
- 46
- References
- 22
- Citations by year
- 2025: 1 · 2024: 1 · 2021: 1 · 2019: 1 · 2018: 5 · 2017: 10 · 2016: 11 · 2015: 5 · 2014: 8 · 2013: 3
- FWCI
- 7.31
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Lung Cancer (publishedVersion)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Brain Metastases and Treatment
- Health Sciences › Medicine › Genetics › Glioma Diagnosis and Treatment
- Keywords
- erlotinib, leptomeningeal metastasis, non-small cell lung cancer, EGFR mutation, blood-brain barrier, cerebrospinal fluid drug concentration, central nervous system metastasis
- MeSH terms
- Erlotinib Hydrochloride, Carcinoma, Non-Small-Cell Lung, Dose-Response Relationship, Drug, Female, Humans, Lung Neoplasms, Middle Aged, Mutation, Quinazolines, Thoracic Diseases, Treatment Outcome, Protein Kinase Inhibitors, Meningeal Carcinomatosis, ErbB Receptors
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