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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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.
KeywordsLeptomeningeal 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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