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High-dose erlotinib for refractory leptomeningeal metastases after failure of standard-dose EGFR-TKIs

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Abstract

Background

After initial response to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), approximately one-third of patients develop central nervous system (CNS) metastases, including leptomeningeal metastases (LM). To achieve longer survival, control of CNS metastases is important, but therapeutic options are limited for LM after failure of standard-dose EGFR-TKIs.

Methods

We retrospectively evaluated the efficacy and safety of high-dose erlotinib in EGFR-mutant non-small cell lung cancer (NSCLC) patients with refractory LM after failure of standard-dose EGFR-TKIs. Survivals from diagnosis of LM to death were compared in patients with or without high-dose erlotinib.

Results

Between January 2007 and April 2013, we identified 35 patients with EGFR-mutant NSCLC, complicated with LM, and 12 underwent high-dose erlotinib, while the other 23 received only standard-dose EGFR-TKIs. In patients receiving high-dose erlotinib, magnetic resonance imaging response was confirmed in 3 (30 %) of 10 evaluable patients. Median time to CNS progression was 2.3 months (95 % confidence interval [CI] 1.8–5.5 months). Performance status and neurological symptoms improved in 4 (33 %) of 12 and 6 (50 %) of 12 patients, respectively. No severe adverse events (≥grade 3) associated with high-dose erlotinib were observed. Median survival time from diagnosis of LM in patients with high-dose erlotinib was 6.2 months (95 % CI 2.5–8.5 months), and in those without 5.9 months (95 % CI 1.3–7.8 months) (p = 0.94).

Conclusion

High-dose erlotinib suggested its efficacy and safety in some patients with refractory LM. It represents a potential therapeutic option against LM after failure of standard-dose EGFR-TKIs, especially to palliate LM-related neurological symptoms.

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Authors and Affiliations

  1. Department of Respiratory Medicine, Kobe City Medical Center General Hospital, Kobe, Japan

    Takahisa Kawamura, Michio Hayashi & Keisuke Tomii

  2. Division of Integrated Oncology, Institute of Biomedical Research and Innovation, 2-2, Minatojima-minamimachi, Chuo-ku, Kobe, 650-0047, Japan

    Akito Hata, Jumpei Takeshita, Shiro Fujita & Nobuyuki Katakami

Authors
  1. Takahisa Kawamura
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  2. Akito Hata
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  3. Jumpei Takeshita
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  4. Shiro Fujita
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  5. Michio Hayashi
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  6. Keisuke Tomii
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  7. Nobuyuki Katakami
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Correspondence to Akito Hata.

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Kawamura, T., Hata, A., Takeshita, J. et al. High-dose erlotinib for refractory leptomeningeal metastases after failure of standard-dose EGFR-TKIs. Cancer Chemother Pharmacol 75, 1261–1266 (2015). https://doi.org/10.1007/s00280-015-2759-y

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  • DOI: https://doi.org/10.1007/s00280-015-2759-y

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