Cerebrospinal Xuid concentration of geWtinib and erlotinib in patients with non-small cell lung cancer

Purpose Several cases have been reported in which central nervous system (CNS) metastases of non-small cell lung cancer (NSCLC) resistant to geWtinib were improved by erlotinib. However, there has been no study in which cerebrospinal Xuid (CSF) concentrations of geWtinib and erlotinib are directly compared. Thus, we aimed to compare them. Methods We examined 15 Japanese patients with NSCLC and CNS metastases with epidermal growth factor receptor gene mutations who received CSF examinations during epidermal growth factor receptor-tyrosine kinase inhibitors treatment (250 mg daily geWtinib or 150 mg daily erlotinib). Plasma and CSF concentrations were determined using high-performance liquid chromatography with tandem mass spectrometry. Results The concentration and penetration rate of geWtinib (mean § standard deviation) in the CSF were 3.7 § 1.9 ng/mL (8.2 § 4.3 nM) and 1.13 § 0.36 %, respectively. The concentration and penetration rate of erlotinib in the CSF were 28.7 § 16.8 ng/mL (66.9 § 39.0 nM) and 2.77 § 0.45 %, respectively. The CSF concentration and penetration rate of erlotinib were signiWcantly higher than those of geWtinib (P = 0.0008 and <0.0001, respectively). The CNS response rates of patients with erlotinib treatment were preferentially (but not signiWcantly) higher than those with geWtinib treatment. (1/3 vs. 4/7, respectively). Leptomeningeal metastases in one patient, which were refractory to geWtinib, dramatically responded to erlotinib. Conclusions This study suggested that higher CSF concentration could be achieved with erlotinib and that erlotinib could be more eVective for the treatment for CNS metastases, especially leptomeningeal metastases, than