title: Clinical pharmacokinetics, safety, and preliminary efficacy evaluation of icotinib in patients with advanced non-small cell lung cancer.
abstract: OBJECTIVE
  To receive pharmacokinetics, safety, and anti-tumor activity of icotinib, a novel epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI), in patients with advanced non-small-cell lung cancer (NSCLC).
  
  
  METHODS
  Patients (n=40) with advanced NSCLC were enrolled to receive escalating doses of icotinib, which was administrated on Day 1 followed by 28-day continuous dosing starting from Day 4. Four dosing regimens, 100mg b.i.d., 150 mg b.i.d., 125 mg t.i.d., and 200mg b.i.d. were studied. Pharmacokinetics (PK), safety, and efficacy of icotinib were evaluated.
  
  
  RESULTS
  Icotinib was well tolerated in Chinese patients with refractory NSCLC. No toxicity with >3 grades were reported in more than 2 patients under any dose levels. One complete response (3%) and 9 partial responses (23%) were received. Total disease control rate could reach at 73% and median progress-free survival (range) was 154 (17-462) days. PK exposure of icotinib increased with increase of dose in NSCLC patients. Food was suggested to increase PK exposure by ∼30%. Mean t1/2β was within 5.31-8.07 h. No major metabolite (>10% plasma exposure of icotinib) was found in NSCLC patients.
  
  
  CONCLUSIONS
  Icotinib with up to 400 mg/day exhibited good tolerance and preliminary antitumor activity in Chinese NSCLC patients. Pharmacokinetics of icotinib and 5 major metabolites were fully investigated in NSCLC patients. Optimized biologic dose (OBD) was finally recommended to be 125 mg t.i.d. for the later clinical study.
authors.affiliation: Clinical Pharmacology Research Center, Peking Union Medical College Hospital & Chinese Academy of Medical Sciences, Beijing 100032, China.
authors.forename: Dongyang
authors.initials: D
authors.lastname: Liu
authors.affiliation: Department of Pulmonary Medicine, Peking Union Medical College Hospital & Chinese Academy of Medical Sciences 100032 Beijing, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Clinical Pharmacology Research Center, Peking Union Medical College Hospital & Chinese Academy of Medical Sciences, Beijing 100032, China.
authors.forename: Yiwen
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Clinical Pharmacology Research Center, Peking Union Medical College Hospital & Chinese Academy of Medical Sciences, Beijing 100032, China.
authors.forename: Ji
authors.initials: J
authors.lastname: Jiang
authors.affiliation: Zhejiang Beta Pharma Inc., Zhejiang, China.
authors.forename: Fenlai
authors.initials: F
authors.lastname: Tan
authors.affiliation: Zhejiang Beta Pharma Inc., Zhejiang, China.
authors.forename: Yingxiang
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Zhejiang Beta Pharma Inc., Zhejiang, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Clinical Pharmacology Research Center, Peking Union Medical College Hospital & Chinese Academy of Medical Sciences, Beijing 100032, China. Electronic address: pei.hu.pumc@gmail.com.
authors.forename: Pei
authors.initials: P
authors.lastname: Hu
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology*; D003131:Combined Modality Therapy; D043844:Crown Ethers / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011799:Quinazolines / Q000494:pharmacology / Q000627:therapeutic use*; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D043844:Crown Ethers; D011799:Quinazolines; C531470:icotinib
keywords: Clinical Pharmacokinetics; Icotinib; NSCLC Patients; Safety, Activity