Cerebrospinal Fluid Concentrations of Gefitinib in Patients With Lung Adenocarcinoma
Cerebrospinal Fluid Concentrations of Gefitinib in Patients With Lung Adenocarcinoma
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DOI：
10.1016/j.cllc.2012.06.004
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发表时间：
2013-03-01
影响因子：
3.6
通讯作者：
Wang, Mengzhao
中科院分区：
文献类型：
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作者：
Zhao, Jing;Chen, Minjiang;Wang, Mengzhao
吉非替尼已在非小细胞肺癌（NSCLC）和脑转移患者中显示出疗效。但关于其在脑脊液中浓度的报道很少。我们测量了22例患者的CSF和血浆中吉非替尼的浓度。结果显示，吉非替尼的CSF浓度较低，CSF中吉非替尼浓度与血浆中吉非替尼浓度呈正相关。本研究表明，非小细胞肺癌和脑转移患者可能受益于增加吉非替尼剂量为新的颅内nerves.Background：表皮生长因子受体（EGFR）酪氨酸激酶抑制剂（TKIs），如吉非替尼和厄洛替尼，有很高的反应和疾病控制率在中枢神经系统（CNS）转移患者。然而，关于吉非替尼渗透到脑脊液（CSF）中的病例报告很少。本研究的目的是调查吉非替尼在中国肺腺癌患者的CSF浓度。方法：选取2007年3月至2010年12月在北京协和医院住院的22例患者。在至少7次吉非替尼给药后，同时采集每例患者的CSF和血浆样本。采用高效液相色谱-串联质谱法测定吉非替尼在脑脊液和血浆中的浓度。分析可能影响吉非替尼渗透的临床因素。结果如下：吉非替尼的平均血浆和CSF浓度分别为491.8 +/- 184.2 ng/mL和6.2 +/- 4.6 ng/mL，CSF-血浆浓度的平均比值为1.3% +/-0.7%。CSF和血浆吉非替尼浓度之间具有良好的相关性（R = 0.556，P = 0.006）。CNS转移的存在与吉非替尼CSF渗透增加相关（1.46% vs. 0.95%; P = 0.042）。结论：吉非替尼在脑脊液中的浓度较低，且与吉非替尼血药浓度显著相关。由于CNS药物暴露不足，颅外病变得到良好控制的患者可能受益于增加吉非替尼剂量治疗新的颅内病变。临床肺癌，第14卷，第2期，188-93（c）2013年爱思唯尔公司。All rights reserved.
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.