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

Yosuke Togashi, Katsuhiro Masago, Masahide Fukudo, Yasuhiro Tsuchido, Chiyuki Okuda, Young Hak Kim, Yasuaki Ikemi, Yuichi Sakamori, Tadashi Mio, Toshiya Katsura, Michiaki Mishima

Research output: Contribution to journalArticlepeer-review

70 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1089-1092
Number of pages4
JournalCancer Chemotherapy and Pharmacology
Volume68
Issue number4
DOIs
Publication statusPublished - Oct 2011
Externally publishedYes

Keywords

  • Central nervous system metastasis
  • Cerebrospinal fluid
  • Epidermal growth factor receptor
  • Erlotinib
  • Non-small cell lung cancer
  • Tyrosine kinase inhibitor

ASJC Scopus subject areas

  • Oncology
  • Toxicology
  • Pharmacology
  • Cancer Research
  • Pharmacology (medical)

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