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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- Clarke, J.L., Pao, W., Wu, N. et al. J Neurooncol (2010) 99: 283. doi:10.1007/s11060-010-0128-6
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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.