Wei Hu1, Wei Wang2, Peinong Yang3, Chao Zhou2, Weifang Yang2, Bo Wu4, Hongsheng Lu5, Haihua Yang2. 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.
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.
Authors: Ladan Saleh-Ebrahimi; Felix Zwicker; Marc W Muenter; Marc Bischof; Katja Lindel; Juergen Debus; Peter E Huber; Falk Roeder Journal: Radiat Oncol Date: 2013-01-24 Impact factor: 3.481