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

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.