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Erlotinib efficacy and cerebrospinal fluid concentration in patients with lung adenocarcinoma developing leptomeningeal metastases during gefitinib therapy

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Abstract

Purpose

We have treated patients with non-small-cell lung cancer (NSCLC) who developed leptomeningeal metastases (LM) during gefitinib therapy, and then found symptomatic improvement following treatment change to erlotinib. Based on this experience, we wondered whether erlotinib could be detected in cerebrospinal fluid (CSF) when it was used for NSCLC patients with LM. This study was conducted to determine erlotinib concentrations in CSF and assess responses to erlotinib in patients with NSCLC developing LM during gefitinib therapy.

Methods

Three advanced NSCLC patients with LM that developed during gefitinib therapy were treated with erlotinib. On day 28 after the initiation of erlotinib treatment, plasma and CSF were obtained and the concentrations of erlotinib in these samples were measured. Eastern Cooperative Oncology Group (ECOG) performance status (PS) and neurologic symptoms were determined.

Results

Erlotinib CSF penetration was 6.3% ± 6.1% (mean ± SD). In cases 1 and 2, we observed improvements in ECOG PS and neurologic symptoms. In case 3, cytological improvement was seen in the CSF. In each patient, deletion of exon 19 or exon 21 L858R mutation of the epidermal growth factor receptor (EGFR) gene was detected in carcinoma cells from the CSF.

Conclusions

We report on 3 patients with NSCLC who had developed LM during gefitinib treatment and showed clinical improvements following change to erlotinib therapy. In all cases, small but measurable penetration of erlotinib into CSF was observed. Because EGFR mutations were detected in all cases, we suggest that erlotinib is a therapeutic option for LM carcinoma cells with EGFR mutations.

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Acknowledgments

This work was supported in part by a Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (JSPS). Nobuoki Kohno has received a research grant from Chugai Pharmaceutical Co., Ltd.

Conflict of interest

All other authors have no conflict of interest.

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Authors and Affiliations

  1. Department of Molecular and Internal Medicine, Graduate School of Biomedical Science, Hiroshima University, 1-2-3 Kasumi Minami-ku, Hiroshima, 734-8551, Japan

    Takeshi Masuda, Noboru Hattori, Hiroshi Iwamoto, Shinichiro Ohshimo, Masashi Kanehara, Nobuhisa Ishikawa, Kazunori Fujitaka, Yoshinori Haruta, Hiroshi Murai & Nobuoki Kohno

  2. Department of Clinical Pharmaceutical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan

    Akinobu Hamada

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  1. Takeshi Masuda
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  2. Noboru Hattori
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  4. Hiroshi Iwamoto
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  9. Yoshinori Haruta
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  11. Nobuoki Kohno
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Correspondence to Noboru Hattori.

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Masuda, T., Hattori, N., Hamada, A. et al. Erlotinib efficacy and cerebrospinal fluid concentration in patients with lung adenocarcinoma developing leptomeningeal metastases during gefitinib therapy. Cancer Chemother Pharmacol 67, 1465–1469 (2011). https://doi.org/10.1007/s00280-011-1555-6

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  • DOI: https://doi.org/10.1007/s00280-011-1555-6

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