内分泌疾病的治疗：小分子酪氨酸激酶抑制剂在甲状腺癌患者中的疗效与毒性：一项系统评价和荟萃分析
Therapy of endocrine disease: response and toxicity of small-molecule tyrosine kinase inhibitors in patients with thyroid carcinoma: a systematic review and meta-analysis.
作者信息
Klein Hesselink E N, Steenvoorden D, Kapiteijn E, Corssmit E P, van der Horst-Schrivers A N A, Lefrandt J D, Links T P, Dekkers O M
机构信息
Department of EndocrinologyDepartment of Internal MedicineDivision of Vascular Medicine, University Medical Center Groningen, University of Groningen, Groningen, The NetherlandsDepartments of EndocrinologyMedical OncologyClinical EpidemiologyC7-99, Leiden University Medical Center, University of Leiden, PO Box 9600, 2300 RC Leiden, The Netherlands Department of EndocrinologyDepartment of Internal MedicineDivision of Vascular Medicine, University Medical Center Groningen, University of Groningen, Groningen, The NetherlandsDepartments of EndocrinologyMedical OncologyClinical EpidemiologyC7-99, Leiden University Medical Center, University of Leiden, PO Box 9600, 2300 RC Leiden, The Netherlands.
Department of EndocrinologyDepartment of Internal MedicineDivision of Vascular Medicine, University Medical Center Groningen, University of Groningen, Groningen, The NetherlandsDepartments of EndocrinologyMedical OncologyClinical EpidemiologyC7-99, Leiden University Medical Center, University of Leiden, PO Box 9600, 2300 RC Leiden, The Netherlands.
出版信息
Eur J Endocrinol. 2015 May;172(5):R215-25. doi: 10.1530/EJE-14-0788. Epub 2015 Jan 8.
CONTEXT
Many tyrosine kinase inhibitors (TKIs) have been studied in patients with thyroid carcinoma (TC). However, the effect and toxicity of various TKIs in differentiated TC (DTC) and medullary TC (MTC) patients have not been directly compared. The aim of the present systematic review and meta-analysis was to systematically summarize response and toxicity of TKIs in TC patients.
METHODS
All major databases were systematically searched for publications on TKIs in TC. Primary endpoint was objective response; secondary endpoints were clinical benefit, percentage TKI dose reduction/discontinuation, hand-foot syndrome, diarrhea, and nausea/vomiting. Meta-analysis was performed using an exact likelihood approach and a logistic regression. Pooled percentages and 95% CIs were reported.
RESULTS
In total, 22 publications were included. For DTC patients, gefitinib induced no objective responses. Pooled percentage was highest for pazopanib, 49 (95% CI 33-64)%, and was 17 (95% CI 12-24)% for sorafenib. For MTC, gefitinib and imatinib induced no objective responses, whereas sunitinib induced objective response in 43 (95% CI 14-77)%. For vandetanib and cabozantinib, these numbers were 40 (95% CI 34-46)% and 27 (95% CI 22-32)% respectively. Clinical benefit was found in 53 (95% CI 48-59)% of DTC patients on sorafenib, and in 84 (95% CI 79-88)% and 55 (95% CI 49-61)% of MTC patients on vandetanib and cabozantinib respectively. All TKIs were associated with considerable toxicity.
CONCLUSION
The currently studied TKIs show a modest response, while side effects are not negligible. Therefore, we suggest to solely consider TKIs in TC patients with rapid progressive disease, for whom the benefits of treatment outweigh toxicity.
背景
许多酪氨酸激酶抑制剂（TKIs）已在甲状腺癌（TC）患者中进行了研究。然而，各种TKIs在分化型TC（DTC）和髓样TC（MTC）患者中的疗效和毒性尚未得到直接比较。本系统评价和荟萃分析的目的是系统总结TKIs在TC患者中的反应和毒性。
方法
系统检索所有主要数据库中关于TC中TKIs的出版物。主要终点是客观反应；次要终点是临床获益、TKIs剂量减少/停药百分比、手足综合征、腹泻以及恶心/呕吐。使用精确似然法和逻辑回归进行荟萃分析。报告合并百分比和95%置信区间。
结果
共纳入22篇出版物。对于DTC患者，吉非替尼未诱导出客观反应。帕唑帕尼的合并百分比最高，为49（95%CI 33 - 64）%，索拉非尼为17（95%CI 12 - 24）%。对于MTC，吉非替尼和伊马替尼未诱导出客观反应，而舒尼替尼诱导出客观反应的比例为43（95%CI 14 - 77）%。对于凡德他尼和卡博替尼，这些数字分别为40（95%CI 34 - 46）%和27（95%CI 22 - 32）%。在服用索拉非尼的DTC患者中，53（95%CI 48 - 59）%有临床获益，在服用凡德他尼和卡博替尼的MTC患者中，分别有84（95%CI 79 - 88）%和55（95%CI 49 - 61）%有临床获益。所有TKIs均与相当大的毒性相关。
结论
目前研究的TKIs显示出适度的反应，而副作用不可忽视。因此，我们建议仅在疾病快速进展的TC患者中考虑使用TKIs，此类患者治疗的获益大于毒性。
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