Cancer Chemotherapy and Pharmacology

, Volume 70, Issue 3, pp 399–405 | Cite as

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
Original Article



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 fluid (CSF) concentrations of gefitinib and erlotinib are directly compared. Thus, we aimed to compare them.


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.


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.


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.


Non-small cell lung cancer Epidermal growth factor receptor gene mutation Gefitinib Erlotinib Cerebrospinal fluid Leptomeningeal metastases 



This research was partially supported by Funding Program for Next Generation World-Leading Researchers (NEXT Program; LS073).

Conflict of interest

The authors have no conflict of interest.


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Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Yosuke Togashi
    • 1
  • Katsuhiro Masago
    • 1
  • Satohiro Masuda
    • 2
  • Tomoyuki Mizuno
    • 2
  • Masahide Fukudo
    • 2
  • Yasuaki Ikemi
    • 2
  • Yuichi Sakamori
    • 1
  • Hiroki Nagai
    • 1
  • Young Hak Kim
    • 1
  • Toshiya Katsura
    • 2
  • Michiaki Mishima
    • 1
  1. 1.Department of Respiratory Medicine, Graduate School of MedicineKyoto UniversityKyotoJapan
  2. 2.Department of Pharmacy, Graduate School of MedicineKyoto University HospitalKyotoJapan

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