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Int J Clin Exp Med. 2015 Sep 15;8(9):15675-83. eCollection 2015.

Phase I study of icotinib, an EGFR tyrosine kinase inhibitor combined with IMRT in nasopharyngeal carcinoma.

Author information

1
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.
2
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.
3
Department of Pathology, Affiliated Taizhou Hospital of Wenzhou Medical University Taizhou 317000, China.
4
Department of Radiation Oncology, Taizhou Central Hospital Taizhou 318000, China.
5
Department of Pathology, Taizhou Central Hospital Taizhou 318000, China.

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.

CONCLUSION:

The combination of icotinib (125 mg/day) and IMRT in patients with locally NPC had an acceptable safety profile and was well tolerated.

KEYWORDS:

Nasopharyngeal carcinoma; dose-limiting toxicity; icotinib hydrochloride; intensity-modulated radiotherapy

PMID:
26629062
PMCID:
PMC4658951

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