埃克替尼（一种表皮生长因子受体酪氨酸激酶抑制剂）联合调强适形放疗用于鼻咽癌的Ⅰ期研究
Phase I study of icotinib, an EGFR tyrosine kinase inhibitor combined with IMRT in nasopharyngeal carcinoma.
作者信息
Hu Wei, Wang Wei, Yang Peinong, Zhou Chao, Yang Weifang, Wu Bo, Lu Hongsheng, Yang Haihua
机构信息
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.
出版信息
Int J Clin Exp Med. 2015 Sep 15;8(9):15675-83. eCollection 2015.
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.
背景
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。
方法
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。
结果
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）。
结论
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。
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