title: Phase I study of icotinib, an EGFR tyrosine kinase inhibitor combined with IMRT in nasopharyngeal carcinoma.
abstract: BACKGROUND
  Epidermal growth factor receptor (EGFR) is a new target for nasopharyngeal carcinoma (NPC) therapy. This prospective phase I study sought to determine the safety and recommended phase II dose of icotinib, a novel highly selective oral EGFR tyrosine kinase inhibitor, in combination with intensity-modulated radiotherapy (IMRT) in patients with NPC.
  
  
  METHODS
  Eligible patients with NPC received escalating doses of icotinib during IMRT. We treated six patients at a particular dose level until the maximum tolerated dose (MTD) was determined. The starting dose was 125 mg, once-daily and the dose was escalated to another level 125 mg, twice- and thrice- daily, until dose-limiting toxicity (DLT) occurred in two or more patients at a dose level. Expression and mutation analysis of EGFR were performed in all cases.
  
  
  RESULTS
  A total of twelve patients were enrolled. Three patients experienced DLT (250 mg/day cohort) and MTD was 125 mg/day. Mucositis toxicity appears to be the major DLT. While EGFR expression in tumor tissue was detected in 75% (9/12) patients, EGFR mutation was detected in 16.67% (1/6) patients in 125 mg/day cohort, and 50% (3/6) in 250 mg/day cohort.
  
  
  CONCLUSIONS
  The combination of icotinib (125 mg/day) and IMRT in patients with locally NPC had an acceptable safety profile and was well tolerated.
authors.affiliation: Department of Radiation Oncology, Affiliated Taizhou Hospital of Wenzhou Medical University Taizhou 317000, China ; Laboratory of Cellular and Molecular Radiation Oncology, Affiliated Taizhou Hospital of Wenzhou Medical University Taizhou 317000, China ; Department of Radiation Oncology, Taizhou Central Hospital Taizhou 318000, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Hu
authors.affiliation: Department of Radiation Oncology, Affiliated Taizhou Hospital of Wenzhou Medical University Taizhou 317000, China ; Laboratory of Cellular and Molecular Radiation Oncology, Affiliated Taizhou Hospital of Wenzhou Medical University Taizhou 317000, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Pathology, Affiliated Taizhou Hospital of Wenzhou Medical University Taizhou 317000, China.
authors.forename: Peinong
authors.initials: P
authors.lastname: Yang
authors.affiliation: Department of Radiation Oncology, Affiliated Taizhou Hospital of Wenzhou Medical University Taizhou 317000, China ; Laboratory of Cellular and Molecular Radiation Oncology, Affiliated Taizhou Hospital of Wenzhou Medical University Taizhou 317000, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Zhou
authors.affiliation: Department of Radiation Oncology, Affiliated Taizhou Hospital of Wenzhou Medical University Taizhou 317000, China ; Laboratory of Cellular and Molecular Radiation Oncology, Affiliated Taizhou Hospital of Wenzhou Medical University Taizhou 317000, China.
authors.forename: Weifang
authors.initials: W
authors.lastname: Yang
authors.affiliation: Department of Radiation Oncology, Taizhou Central Hospital Taizhou 318000, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Wu
authors.affiliation: Department of Pathology, Taizhou Central Hospital Taizhou 318000, China.
authors.forename: Hongsheng
authors.initials: H
authors.lastname: Lu
authors.affiliation: Department of Radiation Oncology, Affiliated Taizhou Hospital of Wenzhou Medical University Taizhou 317000, China ; Laboratory of Cellular and Molecular Radiation Oncology, Affiliated Taizhou Hospital of Wenzhou Medical University Taizhou 317000, China.
authors.forename: Haihua
authors.initials: H
authors.lastname: Yang
keywords: Nasopharyngeal carcinoma; dose-limiting toxicity; icotinib hydrochloride; intensity-modulated radiotherapy