Cerebrospinal Fluid Concentrations of Gefitinib in Patients With Lung Adenocarcinoma

Gefitinib has shown efficacy in patients with non-small-cell lung cancer (NSCLC) and brain metastases. However there have been only a few case reports about its concentration in cerebrospinal fluid (CSF). We measured concentrations of gefitinib in both CSF and plasma in 22 patients. The results showed that the CSF gefitinib concentration was low, and there was a positive correlation between the concentration of gefitinib in CSF and gefitinib in plasma. This study suggested that patients with NSCLC and brain metastases may benefit from increasing the gefitinib dose for new intracranial lesions. Background: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), such as gefitinib and erlotinib, have high response and disease control rates in patients with central nervous system (CNS) metastases. However there have been only a few case reports on the penetration of gefitinib into the cerebrospinal fluid (CSF). The aim of this study was to investigate the CSF concentration of gefitinib in Chinese patients with lung adenocarcinomas. Methods: From March 2007 to December 2010, 22 patients were sequentially enrolled in this study at Peking Union Medical College Hospital (PUMCH). CSF and plasma samples were collected at the same time from each patient after at least 7 doses of gefitinib. The concentrations of gefitinib in the CSF and plasma were measured by high performance liquid chromatography coupled with tandem mass spectrometry. The clinical factors that may affect gefitinib penetration were analyzed. Results: The mean plasma and CSF concentrations of gefitinib were 491.8 +/- 184.2 ng/mL and 6.2 +/- 4.6 ng/mL, respectively, and the mean ratio of CSF-plasma concentration was 1.3% +/- 0.7%. There was a good correlation between CSF and plasma gefitinib concentrations (R = 0.556, P = .006). The presence of CNS metastases was associated with increased gefitinib CSF penetration (1.46% vs. 0.95%; P = .042). Conclusions: The concentration of gefitinib in CSF was low, and it was significantly related to the plasma gefitinib concentration. Because of the inadequate CNS drug exposure, patients in whom the extracranial lesions were well controlled may benefit from increasing gefitinib dose for the new intracranial lesions. Clinical Lung Cancer, Vol. 14, No. 2, 188-93 (c) 2013 Elsevier Inc. All rights reserved.