title: Blood-brain barrier permeability of gefitinib in patients with brain metastases from non-small-cell lung cancer before and during whole brain radiation therapy.
abstract: BACKGROUND
  To explore the ability of gefitinib to penetrate blood brain barrier (BBB) during whole brain radiation therapy (WBRT).
  
  
  METHODS
  Enrolled in this study were eligible patients who were diagnosed with BM from NSCLC. Gefitinib was given at 250 mg/day for 30 days, then concurrently with WBRT (40 Gy/20 F/4 w), followed by maintenance. Serial CSF and blood samples were collected on 30 day after gefitinib administration, and at the time of 10, 20, 30 and 40 Gy following WBRT. CSF and plasma samples of 13 patients without BM who were treated with gefitinib were collected as control. CSF and plasma gefitinib levels were measured by LC-MS/MS.
  
  
  RESULTS
  Fifteen BM patients completed gefitinib plus WBRT. The CSF-to-plasma ratio of gefitinib in patients with BM was higher than that in patients without BM (1.34% vs. 0.36%, P < 0.001). The CSF-to-plasma ratio of gefitinib increased with the increased dose of WBRT and reached the peak (1.87 ± 0.72%) at 30 Gy, which was significantly higher than that 1.34 ± 0.49% at 0 Gy (P = 0.01). The median time to progression of brain lesions and the median overall survival were 7.07 and 15.4 months, respectively.
  
  
  CONCLUSIONS
  The BBB permeability of gefitinib increased in accordance with escalated dose of WBRT.
authors: Department of Medical Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China.
authors: Yin-Duo
authors: YD
authors: Zeng
authors: Lab of Phase I Clinical Study, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China.
authors: Hai
authors: H
authors: Liao
authors: Department of Medical Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China.
authors: Tao
authors: T
authors: Qin
authors: Department of Medical Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China.
authors: Li
authors: L
authors: Zhang
authors: Department of Breast Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China.
authors: Wei-Dong
authors: WD
authors: Wei
authors: Department of Pathology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China.
authors: Jian-Zhong
authors: JZ
authors: Liang
authors: Department of Medical Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China.
authors: Fei
authors: F
authors: Xu
authors: Department of Medical Oncology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China.
authors: Xiao-Xiao
authors: XX
authors: Dinglin
authors: Department of Medical Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China.
authors: Shu-Xiang
authors: SX
authors: Ma
authors: Department of Medical Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China.
authors: Li-Kun
authors: LK
authors: Chen
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000627:therapeutic use; D001812:Blood-Brain Barrier / Q000378:metabolism* / Q000473:pathology; D001932:Brain Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000532:radiotherapy* / Q000556:secondary*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D005260:Female; D000077156:Gefitinib; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011379:Prognosis; D011799:Quinazolines / Q000493:pharmacokinetics* / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D011799:Quinazolines; D000077156:Gefitinib
keywords: blood-brain barrier; brain metastasis; gefitinib; non-small-cell lung cancer; whole brain radiation therapy