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High dose weekly erlotinib achieves therapeutic concentrations in CSF and is effective in leptomeningeal metastases from epidermal growth factor receptor mutant lung cancer

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Abstract

Leptomeningeal metastases (LM) occur in 5–10% of patients with solid tumors and are associated with a dismal prognosis. We describe LM from lung adenocarcinoma harboring a mutation in the epidermal growth factor receptor (EGFR) gene that confers sensitivity to the EGFR tyrosine kinase inhibitors (EGFR-TKIs) erlotinib and gefitinib. The CSF concentration of EGFR-TKIs achieved by standard daily dosing may be insufficient for therapeutic effect. However, intermittent (pulsatile) high dose administration (1000–1500 mg/week) achieves a higher CSF concentration than standard dosing, and successfully controlled LM in this patient.

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Acknowledgements

Marissa Balak for EGFR mutational analysis; Joan’s Legacy, the Doris Duke Charitable Foundation, and the NIH for funding (WP); Lisa M. DeAngelis, MD and Ingo Mellinghoff, MD for critical review of the manuscript; Judith Lampron for invaluable editorial assistance.

Disclaimers

Drs. Pao and Miller report the following potential conflict of interest: a patent on EGFR T790M testing has been licensed on behalf of Drs. Pao, Miller, and others by MSKCC to MolecularMD.

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Author notes

  1. Jennifer L. Clarke

    Present address: Department of Neurological Surgery, Division of Neuro-Oncology, University of California, San Francisco, USA

  2. William Pao

    Present address: Vanderbilt-Ingram Cancer Center, Nashville, TN, USA

Authors and Affiliations

  1. Department of Neurology and Brain Tumor Center, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USA

    Jennifer L. Clarke & Andrew B. Lassman

  2. Thoracic Oncology Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, USA

    William Pao & Vincent A. Miller

  3. Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, USA

    William Pao

  4. Program in Pharmacology, Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center, New York, USA

    Nian Wu

Authors
  1. Jennifer L. Clarke
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  2. William Pao
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  3. Nian Wu
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  4. Vincent A. Miller
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  5. Andrew B. Lassman
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Corresponding author

Correspondence to Andrew B. Lassman.

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Clarke, J.L., Pao, W., Wu, N. et al. High dose weekly erlotinib achieves therapeutic concentrations in CSF and is effective in leptomeningeal metastases from epidermal growth factor receptor mutant lung cancer. J Neurooncol 99, 283–286 (2010). https://doi.org/10.1007/s11060-010-0128-6

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  • DOI: https://doi.org/10.1007/s11060-010-0128-6

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