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Efficacy of increased-dose erlotinib for central nervous system metastases in non-small cell lung cancer patients with epidermal growth factor receptor mutation

PURPOSE: Recent reports indicate that refractory central nervous system (CNS) metastases of non-small cell lung cancer (NSCLC) are improved by high-dose gefitinib or erlotinib administration. We describe a Japanese woman with NSCLC and CNS metastases who was resistant to 75 mg daily erlotinib, but t...

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Autores principales: Togashi, Yosuke, Masago, Katsuhiro, Fukudo, Masahide, Tsuchido, Yasuhiro, Okuda, Chiyuki, Kim, Young Hak, Ikemi, Yasuaki, Sakamori, Yuichi, Mio, Tadashi, Katsura, Toshiya, Mishima, Michiaki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer-Verlag 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3180562/
https://www.ncbi.nlm.nih.gov/pubmed/21681573
http://dx.doi.org/10.1007/s00280-011-1691-z
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author Togashi, Yosuke
Masago, Katsuhiro
Fukudo, Masahide
Tsuchido, Yasuhiro
Okuda, Chiyuki
Kim, Young Hak
Ikemi, Yasuaki
Sakamori, Yuichi
Mio, Tadashi
Katsura, Toshiya
Mishima, Michiaki
author_facet Togashi, Yosuke
Masago, Katsuhiro
Fukudo, Masahide
Tsuchido, Yasuhiro
Okuda, Chiyuki
Kim, Young Hak
Ikemi, Yasuaki
Sakamori, Yuichi
Mio, Tadashi
Katsura, Toshiya
Mishima, Michiaki
author_sort Togashi, Yosuke
collection PubMed
description PURPOSE: Recent reports indicate that refractory central nervous system (CNS) metastases of non-small cell lung cancer (NSCLC) are improved by high-dose gefitinib or erlotinib administration. We describe a Japanese woman with NSCLC and CNS metastases who was resistant to 75 mg daily erlotinib, but the metastases were improved by 150 mg daily erlotinib. We investigated the plasma and CSF concentrations of erlotinib at each dose as well as the correlation between the plasma and CSF concentrations of erlotinib. METHODS: Including this patient, we administered 150 mg erlotinib daily to nine NSCLC patients with CNS metastases and measured the plasma and CSF concentrations just before administration on day 8. The concentrations were determined using high-performance liquid chromatography with ultraviolet detection. RESULTS: The plasma and CSF concentrations of erlotinib at a dose of 75 mg were 433 and 14 nM, respectively. The plasma and CSF concentrations of erlotinib at a dose of 150 mg were increased to 1,117 and 44 nM, respectively. The mean ± standard deviation of CSF concentrations and penetration rates were 106 ± 59 nM and 4.5 ± 1.5%, respectively. There was a good correlation (R (2) = 0.84) between plasma and CSF concentrations (P = 0.0005). CONCLUSIONS: This study indicates that CSF concentrations of erlotinib depend on its plasma concentration. As seen in this patient, high CSF concentrations of erlotinib can be achieved by high-dose administration, and this finding suggests the efficacy of high-dose administration, especially to refractory CNS metastases of NSCLC patients.
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spelling pubmed-31805622011-10-04 Efficacy of increased-dose erlotinib for central nervous system metastases in non-small cell lung cancer patients with epidermal growth factor receptor mutation Togashi, Yosuke Masago, Katsuhiro Fukudo, Masahide Tsuchido, Yasuhiro Okuda, Chiyuki Kim, Young Hak Ikemi, Yasuaki Sakamori, Yuichi Mio, Tadashi Katsura, Toshiya Mishima, Michiaki Cancer Chemother Pharmacol Short Communication PURPOSE: Recent reports indicate that refractory central nervous system (CNS) metastases of non-small cell lung cancer (NSCLC) are improved by high-dose gefitinib or erlotinib administration. We describe a Japanese woman with NSCLC and CNS metastases who was resistant to 75 mg daily erlotinib, but the metastases were improved by 150 mg daily erlotinib. We investigated the plasma and CSF concentrations of erlotinib at each dose as well as the correlation between the plasma and CSF concentrations of erlotinib. METHODS: Including this patient, we administered 150 mg erlotinib daily to nine NSCLC patients with CNS metastases and measured the plasma and CSF concentrations just before administration on day 8. The concentrations were determined using high-performance liquid chromatography with ultraviolet detection. RESULTS: The plasma and CSF concentrations of erlotinib at a dose of 75 mg were 433 and 14 nM, respectively. The plasma and CSF concentrations of erlotinib at a dose of 150 mg were increased to 1,117 and 44 nM, respectively. The mean ± standard deviation of CSF concentrations and penetration rates were 106 ± 59 nM and 4.5 ± 1.5%, respectively. There was a good correlation (R (2) = 0.84) between plasma and CSF concentrations (P = 0.0005). CONCLUSIONS: This study indicates that CSF concentrations of erlotinib depend on its plasma concentration. As seen in this patient, high CSF concentrations of erlotinib can be achieved by high-dose administration, and this finding suggests the efficacy of high-dose administration, especially to refractory CNS metastases of NSCLC patients. Springer-Verlag 2011-06-17 2011 /pmc/articles/PMC3180562/ /pubmed/21681573 http://dx.doi.org/10.1007/s00280-011-1691-z Text en © The Author(s) 2011 https://creativecommons.org/licenses/by-nc/4.0/ This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.
spellingShingle Short Communication
Togashi, Yosuke
Masago, Katsuhiro
Fukudo, Masahide
Tsuchido, Yasuhiro
Okuda, Chiyuki
Kim, Young Hak
Ikemi, Yasuaki
Sakamori, Yuichi
Mio, Tadashi
Katsura, Toshiya
Mishima, Michiaki
Efficacy of increased-dose erlotinib for central nervous system metastases in non-small cell lung cancer patients with epidermal growth factor receptor mutation
title Efficacy of increased-dose erlotinib for central nervous system metastases in non-small cell lung cancer patients with epidermal growth factor receptor mutation
title_full Efficacy of increased-dose erlotinib for central nervous system metastases in non-small cell lung cancer patients with epidermal growth factor receptor mutation
title_fullStr Efficacy of increased-dose erlotinib for central nervous system metastases in non-small cell lung cancer patients with epidermal growth factor receptor mutation
title_full_unstemmed Efficacy of increased-dose erlotinib for central nervous system metastases in non-small cell lung cancer patients with epidermal growth factor receptor mutation
title_short Efficacy of increased-dose erlotinib for central nervous system metastases in non-small cell lung cancer patients with epidermal growth factor receptor mutation
title_sort efficacy of increased-dose erlotinib for central nervous system metastases in non-small cell lung cancer patients with epidermal growth factor receptor mutation
topic Short Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3180562/
https://www.ncbi.nlm.nih.gov/pubmed/21681573
http://dx.doi.org/10.1007/s00280-011-1691-z
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