title: A phase II study of icotinib and whole-brain radiotherapy in Chinese patients with brain metastases from non-small cell lung cancer.
abstract: OBJECTIVE
  Icotinib is a new first-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors. A phase II study was conducted to evaluate the efficacy and safety of icotinib in combination with whole-brain radiotherapy (WBRT) in Chinese NSCLC patients with brain metastases (BMs); the cerebrospinal fluid (CSF)/plasma concentrations of icotinib were also investigated.
  
  
  METHODS
  Eligible patients had BMs from NSCLC, regardless of the EGFR status. Icotinib was administered at 125 mg orally 3 times/day until tumor progression or unacceptable toxicity, concurrently with WBRT (3.0 Gy per day, 5 days per week, to 30 Gy). CSF and plasma samples were collected simultaneously from 10 patients. Icotinib concentrations in the CSF and plasma were measured by high-performance liquid chromatography coupled with tandem mass spectrometry.
  
  
  RESULTS
  Twenty patients were enrolled. The median follow-up time was 20.0 months. The overall response rate was 80.0%. The median progression-free survival time was 7.0 months (95% CI 1.2-13.2 months), and the median survival time (MST) was 14.6 months (95% CI 12.5-16.7 months). Of the 18 patients with known EGFR status, the MST was 22.0 months for those with an EGFR mutation and was 7.5 months for those with wild-type EGFR (P = 0.0001). The CSF concentration and penetration rate of icotinib were 11.6 ± 9.1 ng/mL and 1.4 ± 1.1%, respectively. No patient experienced ≥grade 4 toxicity.
  
  
  CONCLUSIONS
  Icotinib was well tolerated in combination with WBRT and showed efficacy in patients with BMs from NSCLC. This clinical benefit was related to the presence of activating EGFR mutations.
authors.affiliation: Key Laboratory Diagnosis and Treatment Technology on Thoracic Oncology (Esophagus, Lung), Zhejiang Cancer Hospital, 38 Guangji Road, Hangzhou, 310022, Zhejiang, People's Republic of China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Fan
authors.forename: Zhiyu
authors.initials: Z
authors.lastname: Huang
authors.forename: Luo
authors.initials: L
authors.lastname: Fang
authors.forename: Lulu
authors.initials: L
authors.lastname: Miao
authors.forename: Lei
authors.initials: L
authors.lastname: Gong
authors.forename: Haifeng
authors.initials: H
authors.lastname: Yu
authors.forename: Haiyan
authors.initials: H
authors.lastname: Yang
authors.forename: Tao
authors.initials: T
authors.lastname: Lei
authors.forename: Weimin
authors.initials: W
authors.lastname: Mao
mesh_terms: D000328:Adult; D000368:Aged; 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 / Q000532:radiotherapy*; D059248:Chemoradiotherapy; D043844:Crown Ethers / Q000097:blood / Q000134:cerebrospinal fluid / Q000627:therapeutic use*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011799:Quinazolines / Q000097:blood / Q000134:cerebrospinal fluid / Q000627:therapeutic use*
chemical_list: D043844:Crown Ethers; D011799:Quinazolines; C531470:icotinib