Journal of Neuro-Oncology

, Volume 99, Issue 2, pp 283–286 | Cite as

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

  • Jennifer L. Clarke
  • William Pao
  • Nian Wu
  • Vincent A. Miller
  • Andrew B. Lassman
Case Report


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.


Leptomeningeal metastases EGFR Lung cancer Erlotinib 



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.


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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Copyright information

© Springer Science+Business Media, LLC. 2010

Authors and Affiliations

  • Jennifer L. Clarke
    • 1
    • 2
  • William Pao
    • 3
    • 4
    • 5
  • Nian Wu
    • 6
  • Vincent A. Miller
    • 3
  • Andrew B. Lassman
    • 1
  1. 1.Department of Neurology and Brain Tumor CenterMemorial Sloan-Kettering Cancer CenterNew YorkUSA
  2. 2.Department of Neurological Surgery, Division of Neuro-OncologyUniversity of CaliforniaSan FranciscoUSA
  3. 3.Thoracic Oncology Service, Department of MedicineMemorial Sloan-Kettering Cancer CenterNew YorkUSA
  4. 4.Human Oncology and Pathogenesis ProgramMemorial Sloan-Kettering Cancer CenterNew YorkUSA
  5. 5.Vanderbilt-Ingram Cancer CenterNashvilleUSA
  6. 6.Program in PharmacologySloan-Kettering Institute, Memorial Sloan-Kettering Cancer CenterNew YorkUSA

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