PMID- 21144613
OWN - NLM
STAT- MEDLINE
DCOM- 20111121
LR  - 20220316
IS  - 1872-8332 (Electronic)
IS  - 0169-5002 (Linking)
VI  - 73
IP  - 2
DP  - 2011 Aug
TI  - Phase I study of icotinib hydrochloride (BPI-2009H), an oral EGFR tyrosine kinase 
      inhibitor, in patients with advanced NSCLC and other solid tumors.
PG  - 195-202
LID - 10.1016/j.lungcan.2010.11.007 [doi]
AB  - PURPOSE: The goal of this study was to assess the safety and tolerability of 
      icotinib hydrochloride (BPI-2009H), a new selective epidermal growth factor 
      receptor tyrosine kinase inhibitor (EGFR TKI), and to explore its 
      pharmacokinetics (PK) and clinical activity in patients with advanced solid 
      tumors, mainly those with non-small-cell lung cancer (NSCLC) after the failure of 
      the prior platinum-based chemotherapy. EXPERIMENTAL DESIGN: Different doses of 
      oral icotinib were administered once every 8 h (Q8H) for a 28-continuous-day 
      cycle until disease progression and or undue toxicity was observed. PK studies of 
      subjects' blood were performed during cycle one (day 1 through 28). Patients aged 
      >/=18 and </=70 years with an Eastern Cooperative Oncology Group (ECOG) performance 
      status (PS) of 0-1 and adequate organ functions eligible for the study. Tumor 
      responses were assessed by Response Evaluation Criteria in Solid Tumors (RECIST). 
      K-ras and EGFR mutations in the extracted DNA of fourteen specimens were examined 
      using PCR-based direct sequencing assay. RESULTS: Thirty-six patients were 
      enrolled in the study. PK analysis demonstrated that the mean elimination 
      half-life of icotinib was 6 h, and the T(max) was around 2 h. The steady-state 
      concentration of icotinib administered at a dose of 125 mg once every 8 h (Q8H) 
      was significantly higher than that achieved by a dose of 100mg Q8H. The most 
      frequent treatment-related adverse events (TRAEs) were an acne-like 
      (folliculitis) rash (16/36, 44.4%), diarrhea (8/36, 22.2%) and a decrease in 
      white blood cells (4/36, 11.1%). The maximum-tolerated dose (MTD) was not 
      reached. Among 33 patients with NSCLC, 7 patients exhibited a partial response, 7 
      showed stable disease at the 24 weeks. Among 14 patients undergoing DNA sequence 
      for K-ras and EGFR mutations, 3 with K-ras mutation presented 2 stable disease 
      (SD) and 1 partial response (PR), 5 with EGFR exon 19 or 21 mutation 2 PR and 3 
      SD within 4 weeks. CONCLUSIONS: Oral icotinib was generally well tolerated, with 
      manageable and reversible adverse events (AEs) and showed positive clinical 
      anti-tumor activities in patients with advanced NSCLC. The recommended dose for 
      phase II/III studies with icotinib is 125 mg or 150 mg Q8H.
CI  - Copyright (c) 2010 Elsevier Ireland Ltd. All rights reserved.
FAU - Zhao, Qiong
AU  - Zhao Q
AD  - Department of Respiratory Disease, The First Affiliated Hospital, Zhejiang 
      University, School of Medicine, No. 79, Qingchun Road, Hangzhou, Zhejiang, China.
FAU - Shentu, Jianzhong
AU  - Shentu J
FAU - Xu, Nong
AU  - Xu N
FAU - Zhou, Jianya
AU  - Zhou J
FAU - Yang, Guangdie
AU  - Yang G
FAU - Yao, Yinan
AU  - Yao Y
FAU - Tan, Fenlai
AU  - Tan F
FAU - Liu, Dongyang
AU  - Liu D
FAU - Wang, Yingxiang
AU  - Wang Y
FAU - Zhou, Jianying
AU  - Zhou J
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Journal Article
DEP - 20101208
PL  - Ireland
TA  - Lung Cancer
JT  - Lung cancer (Amsterdam, Netherlands)
JID - 8800805
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Crown Ethers)
RN  - 0 (Quinazolines)
RN  - 9G6U5L461Q (icotinib)
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - EC 3.6.5.2 (Proto-Oncogene Proteins p21(ras))
SB  - IM
MH  - Administration, Oral
MH  - Adult
MH  - Aged
MH  - Antineoplastic Agents/adverse effects/blood/*therapeutic use
MH  - Carcinoma, Non-Small-Cell Lung/*drug therapy
MH  - Crown Ethers/adverse effects/blood/*therapeutic use
MH  - ErbB Receptors/*antagonists & inhibitors/genetics
MH  - Female
MH  - Folliculitis/chemically induced
MH  - Humans
MH  - Lung Neoplasms/*drug therapy
MH  - Male
MH  - Maximum Tolerated Dose
MH  - Middle Aged
MH  - Proto-Oncogene Proteins p21(ras)/genetics
MH  - Quinazolines/adverse effects/blood/*therapeutic use
MH  - Treatment Outcome
EDAT- 2010/12/15 06:00
MHDA- 2011/12/13 00:00
CRDT- 2010/12/15 06:00
PHST- 2010/08/02 00:00 [received]
PHST- 2010/10/26 00:00 [revised]
PHST- 2010/11/06 00:00 [accepted]
PHST- 2010/12/15 06:00 [entrez]
PHST- 2010/12/15 06:00 [pubmed]
PHST- 2011/12/13 00:00 [medline]
AID - S0169-5002(10)00542-8 [pii]
AID - 10.1016/j.lungcan.2010.11.007 [doi]
PST - ppublish
SO  - Lung Cancer. 2011 Aug;73(2):195-202. doi: 10.1016/j.lungcan.2010.11.007. Epub 
      2010 Dec 8.