Hu Wei, Wang Wei, Yang Peinong, Zhou Chao, Yang Weifang, Wu Bo, Lu Hongsheng, Yang Haihua
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.
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.
Int J Clin Exp Med. 2015 Sep 15;8(9):15675-83. eCollection 2015.
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.
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.
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.
The combination of icotinib (125 mg/day) and IMRT in patients with locally NPC had an acceptable safety profile and was well tolerated.
表皮生长因子受体（EGFR）是鼻咽癌（NPC）治疗的新靶点。这项前瞻性I期研究旨在确定新型高选择性口服EGFR酪氨酸激酶抑制剂埃克替尼与调强放疗（IMRT）联合应用于NPC患者的安全性及推荐的II期剂量。
符合条件的NPC患者在IMRT期间接受递增剂量的埃克替尼治疗。我们在特定剂量水平治疗6例患者，直至确定最大耐受剂量（MTD）。起始剂量为125mg，每日1次，剂量递增至另一个水平，即每日2次和3次，每次125mg，直至在某一剂量水平有两名或更多患者出现剂量限制性毒性（DLT）。对所有病例进行EGFR的表达和突变分析。
共纳入12例患者。3例患者出现DLT（250mg/天队列），MTD为125mg/天。粘膜炎毒性似乎是主要的DLT。虽然75%（9/12）的患者肿瘤组织中检测到EGFR表达，但125mg/天队列中16.67%（1/6）的患者检测到EGFR突变，250mg/天队列中为50%（3/6）。
埃克替尼（125mg/天）与IMRT联合应用于局部NPC患者具有可接受的安全性，耐受性良好。
