title: Whole-brain radiation fails to boost intracerebral gefitinib concentration in patients with brain metastatic non-small cell lung cancer: a self-controlled, pilot study.
abstract: OBJECTIVE
  Whole-brain radiation therapy (WBRT) is generally considered as an efficient strategy to improve blood-brain barrier (BBB) permeability by damaging BBB structure and is therefore, used as a promising pretreatment of chemotherapy. However, the impact of radiotherapy on leaky BBB is still controversial for the reason that BBB of metastatic brain tumor lesion had been breached by tumor metastasizing. Herein, we conducted a self-controlled study to evaluate the effect of WBRT on the permeability of BBB in non-small cell lung cancer (NSCLC) patients with brain metastases (BM).
  
  
  METHODS
  A prospective self-controlled research was performed. Radiation-naive NSCLC patients with BM were enrolled and treated with gefitinib for 2 weeks, and then concurrently combined with WBRT for 2 weeks. Plasma and cerebrospinal fluid (CSF) before and after WBRT were collected on day 15 and 29 after the initiation of gefitinib treatment. The concentrations of gefitinib in these samples were measured by HPLC.
  
  
  RESULTS
  Three patients were enrolled and evaluated. The concentrations of gefitinib in plasma and CSF pre-WBRT were comparable to those of post-WBRT. Consequently, no significant change was noted in the CSF-to-plasma ratios of gefitinib before and after WBRT (2.79 ± 1.47 vs. 2.35 ± 1.74 %, p = 0.123).
  
  
  CONCLUSIONS
  The WBRT may not affect the BBB permeability by determining the concentration of gefitinib in NSCLC patients with BM.
authors: Laboratory of Clinical Pharmacy, Zhejiang Cancer Hospital, Hangzhou, Zhejiang, China.|Zhejiang Key Laboratory of Diagnosis and Treatment Technology on Thoracic Oncology (Lung and Esophagus), Hangzhou, Zhejiang, China.
authors: Luo
authors: L
authors: Fang
authors: Zhejiang Key Laboratory of Diagnosis and Treatment Technology on Thoracic Oncology (Lung and Esophagus), Hangzhou, Zhejiang, China.|Department of Radiation Oncology, Zhejiang Cancer Hospital, Hangzhou, Zhejiang, China.
authors: Xiaojiang
authors: X
authors: Sun
authors: Laboratory of Clinical Pharmacy, Zhejiang Cancer Hospital, Hangzhou, Zhejiang, China.
authors: Yu
authors: Y
authors: Song
authors: Laboratory of Clinical Pharmacy, Zhejiang Cancer Hospital, Hangzhou, Zhejiang, China.
authors: Yiwen
authors: Y
authors: Zhang
authors: College of Pharmaceutical Science, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China.
authors: Fanzhu
authors: F
authors: Li
authors: Zhejiang Key Laboratory of Diagnosis and Treatment Technology on Thoracic Oncology (Lung and Esophagus), Hangzhou, Zhejiang, China.|Department of Radiation Oncology, Zhejiang Cancer Hospital, Hangzhou, Zhejiang, China.
authors: Yaping
authors: Y
authors: Xu
authors: Department of Radiation Oncology, Affiliated Hangzhou Hospital of Nanjing Medical University, Hangzhou, Zhejiang, China. mashenglin@medmail.com.cn.
authors: Shenglin
authors: S
authors: Ma
authors: Institute for Individualized Medicine, Hangzhou First People's Hospital, Hangzhou, Zhejiang, China. lnm1013@163.com.
authors: Nengming
authors: N
authors: Lin
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000097:blood / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects*; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects*; D001932:Brain Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000532:radiotherapy* / Q000556:secondary; D002199:Capillary Permeability / Q000187:drug effects / Q000528:radiation effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood / Q000134:cerebrospinal fluid / Q000188:drug therapy* / Q000556:secondary; D003131:Combined Modality Therapy; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D005260:Female; D000077156:Gefitinib; D006801:Humans; D008175:Lung Neoplasms / Q000097:blood / Q000134:cerebrospinal fluid / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D010865:Pilot Projects; D011446:Prospective Studies; D047428:Protein Kinase Inhibitors / Q000378:metabolism / Q000493:pharmacokinetics / Q000627:therapeutic use; D011799:Quinazolines / Q000097:blood / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics* / Q000627:therapeutic use; D014018:Tissue Distribution / Q000528:radiation effects
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; C512478:EGFR protein, human; D066246:ErbB Receptors; D000077156:Gefitinib
keywords: Blood–brain barrier; Brain metastases; Gefitinib; Non-small cell lung cancer; Whole-brain radiation therapy