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

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Abstract

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 fluid (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.

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Acknowledgments

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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Authors and Affiliations

  1. Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, 54 Shogoin-Kawaharacho, Sakyo-ku, Kyoto, 606-8507, Japan

    Yosuke Togashi, Katsuhiro Masago, Yuichi Sakamori, Hiroki Nagai, Young Hak Kim & Michiaki Mishima

  2. Department of Pharmacy, Graduate School of Medicine, Kyoto University Hospital, 54 Shogoin-Kawaharacho, Sakyo-ku, Kyoto, 606-8507, Japan

    Satohiro Masuda, Tomoyuki Mizuno, Masahide Fukudo, Yasuaki Ikemi & Toshiya Katsura

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  1. Yosuke Togashi
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Correspondence to Yosuke Togashi.

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Togashi, Y., Masago, K., Masuda, S. et al. Cerebrospinal fluid concentration of gefitinib and erlotinib in patients with non-small cell lung cancer. Cancer Chemother Pharmacol 70, 399–405 (2012). https://doi.org/10.1007/s00280-012-1929-4

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  • DOI: https://doi.org/10.1007/s00280-012-1929-4

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