分子靶向药物治疗晚期胃肠道间质瘤的安全性及有效性分析

目的 系统评价分子靶向药物——伊马替尼、舒尼替尼、瑞戈非尼、尼洛替尼和帕唑帕尼对比安慰剂或最佳支持治疗治疗晚期或转移性胃肠道间质瘤（gastrointestinal stromal tumour，GIST）的有效性与安全性。方法 计算机检索Pubmed、Embase、Cochrane Library、中国知网、万方数据库和维普等数据库，按照文献纳入标准和排除标准选择应用分子靶向药物治疗GIST的临床研究，RevMan 5.3软件进行meta分析。其中，试验组为近年来相继上市的酪氨酸激酶抑制剂分子靶向药物——伊马替尼、舒尼替尼、瑞戈非尼、尼洛替尼和帕唑帕尼，对照组为安慰剂或最佳支持治疗。观察终点包括无进展生存期（progression-free survival，PFS）、总生存期（overall survival，OS）和3~4级不良反应发生率。结果 共纳入7项临床研究，总样本量为1 528例。Meta分析结果显示，分子靶向药物与对照组相比，PFS时间（HR=0.34，95%CI：0.26~0.44，P<0.001），OS时间（HR=0.38，95%CI：0.17~0.85，P<0.02）均明显延长。在不良反应方面，分子靶向药物组可使3~4级不良反应（RR=4.47，95%CI：2.12~9.39，P<0.000 1）的发生率明显增高，主要是中性粒细胞减少、高血压、手足综合征、皮疹、腹泻和疲劳。结论 分子靶向药物治疗晚期或转移性GIST可以延长患者的PFS和OS。虽然其不良反应发生率高于对照组，但患者仍可耐受。

Efficacy and Safety of Molecular Targeted Therapy for Gastrointestinal Stromal Tumors: A Meta-Analysis

OBJECTIVE To evaluate the efficacy and safety of the molecular targeted therapeutic drugs for gastrointestinal stromal tumors treatment. METHODS Databases including Pubmed, Embase, Web of Science and China National Knowledge Infrastructure (CNKI) were searched for randomized controlled trials of molecular targeted GIST treatment study. The software adopted was RevMan 5.3. The experimental group were treated with different receptor kinase inhibitors (imatinib, sunitinib, regorafenib, nilotinib and pazopanib). While the control group were given by placebo or best supportive care. The primary endpoint of this study included progression-free survival (PFS), overall survival (OS) and grade 3-4 adverse events (AE). RESULTS Seven randomized controlled trials were selected, with 1 528 patients. Overall improvement was significant for PFS(HR=0.34, 95%C1 0.26-0.44, P<0.001), OS (HR=0.38, 95%CI 0.17-0.85, P<0.02). Grade 3-4 AEs with a significantly increased incidence included(neutrophil reduction, hypertension, hand and foot syndrome, rash, diarrhea and fatigue) (RR=4.47, 95%CI:2.12-9.39, P<0.000 1). CONCLUSION Overall, molecular targeted therapeutic drugs were effective in advanced or metastatic GIST patients by improving the PFS and OS. Although the rate of AE is higher compared to the control group, the toxicity is limited.