Abstract:

Management strategies for advanced gastrointestinal stromal tumors after failure of imatinib        SU Xiang-qian, YANG Hong. Department of Minimally Invasive Gastrointestinal Surgery，Beijing Cancer Hospital & Institute, Peking University Cancer Hospital，Peking University School of Oncology，Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education)，Beijing 100142，China
Corresponding author: SU Xiang-qian，E-mail: suxiangqian@bjmu.edu.cn
Abstract    Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors of the digestive tract. Imatinib is presently the standard first-line therapy for patients with metastatic or unresectable GIST. As entering the clinical arena in the last decade, imatinib substantially improved the outcome in the formerly untreatable carcinomas. However, most advanced GIST responding to imatinib will progress within 2-3 years due to heterogeneous subclones harboring a range of imatinib-resistant secondary c-kit mutations. Sunitinib and more recently regorafenib, have obtained US Food and Drug Administration approval for the treatment of GIST after imatinib failure, and thus expanded the treatment options in resistant disease. Patients with metastatic GIST who have focal resistance to tyrosine kinase inhibitor therapy may bene?t from surgical cytoreduction. Furthermore, surgery may also provide palliation in certain patients with advanced disease who experience intestinal obstruction, perforation or hemorrhage.

Key words: gastrointestinal stromal tumors, imatinib-resistant, sunitinib, regorafenib, cytoreduction

摘要：

胃肠间质瘤（GIST）是消化道最常见的间叶组织来源肿瘤。目前伊马替尼是转移或不可切除GIST的标准一线治疗药物。近10年随着伊马替尼进入GIST的治疗领域，以往不可治愈GIST病人的预后得到明显改善。然而，多数伊马替尼初始治疗有效的晚期GIST，会在2～3年内发展成伊马替尼继发耐药，原因可能与肿瘤中存在继发c-kit基因突变的多细胞克隆有关。舒尼替尼和新近的瑞格非尼均已获美国食品药品监督管理局（FDA）批准分别用于伊马替尼治疗失败的GIST二线和三线治疗，从而拓展了伊马替尼耐药GIST的治疗选择。对于酪氨酸激酶抑制剂治疗基础上出现局部进展的转移GIST，减瘤手术可使病人获益。对于伴发急性肠梗阻、穿孔或出血的晚期GIST，手术可减轻病人症状。

关键词: 胃肠间质瘤, 伊马替尼耐药, 舒尼替尼, 瑞格非尼, 减瘤手术