Cerebrospinal fluid concentration of gefitinib and erlotinib in patients with non-small cell lung cancer

Yosuke Togashi, Katsuhiro Masago, Satohiro Masuda, Tomoyuki Mizuno, Masahide Fukudo, Yasuaki Ikemi, Yuichi Sakamori, Hiroki Nagai, Young Hak Kim, Toshiya Katsura, Michiaki Mishima

Research output: Contribution to journalArticlepeer-review

241 Citations (Scopus)


Purpose Several cases have been reported in which central nervous system (CNS) metastases of non-small cell lung cancer (NSCLC) resistant to gefitinib were improved by erlotinib. However, there has been no study in which cerebrospinal flid (CSF) concentrations of gefitinib and erlotinib are directly compared. Thus, we aimed to compare them. Methods We examined 15 Japanese patients with NSCLC and CNS metastases with epidermal growth factor receptor gene mutations who received CSF examinations during epidermal growth factor receptor-tyrosine kinase inhibitors treatment (250 mg daily gefitinib or 150 mg daily erlotinib). Plasma and CSF concentrations were determined using high-performance liquid chromatography with tandem mass spectrometry. Results The concentration and penetration rate of gefitinib (mean ± standard deviation) in the CSF were 3.7 ± 1.9 ng/mL (8.2 ± 4.3 nM) and 1.13 ± 0.36 %, respectively. The concentration and penetration rate of erlotinib in the CSF were 28.7 ± 16.8 ng/mL (66.9 ± 39.0 nM) and 2.77 ± 0.45 %, respectively. The CSF concentration and penetration rate of erlotinib were significantly higher than those of gefitinib (P = 0.0008 and <0.0001, respectively). The CNS response rates of patients with erlotinib treatment were preferentially (but not significantly) higher than those with gefitinib treatment. (1/3 vs. 4/7, respectively). Leptomeningeal metastases in one patient, which were refractory to gefitinib, dramatically responded to erlotinib. Conclusions This study suggested that higher CSF concentration could be achieved with erlotinib and that erlotinib could be more effective for the treatment for CNS metastases, especially leptomeningeal metastases, than gefitinib.

Original languageEnglish
Pages (from-to)399-405
Number of pages7
JournalCancer chemotherapy and pharmacology
Issue number3
Publication statusPublished - Sept 2012
Externally publishedYes

All Science Journal Classification (ASJC) codes

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


Dive into the research topics of 'Cerebrospinal fluid concentration of gefitinib and erlotinib in patients with non-small cell lung cancer'. Together they form a unique fingerprint.

Cite this