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.
Clarke
Jennifer L
JL
Department of Neurology and Brain Tumor Center, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA.
Pao
William
W
Wu
Nian
N
Miller
Vincent A
VA
Lassman
Andrew B
AB
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000235:genetics / Q000556:secondary; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000134:cerebrospinal fluid / Q000235:genetics*; D000069347:Erlotinib Hydrochloride; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D008297:Male; D008577:Meningeal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000556:secondary; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage* / Q000097:blood / Q000134:cerebrospinal fluid; D011799:Quinazolines / Q000008:administration & dosage* / Q000097:blood / Q000134:cerebrospinal fluid; D016896:Treatment Outcome
D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D000069347:Erlotinib Hydrochloride; C512478:EGFR protein, human; D066246:ErbB Receptors