乐伐替尼治疗放射性碘难治性甲状腺癌的研究进展
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摘要
背景:乐伐替尼是一种多靶点受体酪氨酸激酶抑制剂,欧洲药品管理局(EMA)以及美国食品药品监督管理局(FDA)已于2015年批准乐伐替尼用于治疗甲状腺癌,尤其是局部复发或转移性、进行性、放射性碘难治性分化型甲状腺癌的患者~([1])。且2017年12月,乐伐替尼作为抗肝癌制剂被中国国家食品药品监督管理总局授予优先审批评审资格。本文主要就目前乐伐替尼在甲状腺癌中的临床研究进展进行讨论。笔者从Pubmed,Cochrane Library,EMBASE、中国国家知识基础设施数据库以及万方数据库进行了检索,然后对检索结果进行分析,以此对乐伐替尼治疗放射性碘难治性分化型甲状腺癌的无进展生存期(PFS)、客观应答率(ORR)和不良事件进行研究。目前的临床研究显示,乐伐替尼延长了放射性碘难治性分化型甲状腺癌患者的PFS,提升了ORR。高血压、腹泻、乏力或疲劳、食欲不振、体重下降等是其最常见的副作用。得出乐伐替尼可显著改善放射性碘难治性分化型甲状腺癌患者的PFS及ORR。尽管具有一些副作用,但它目前仍然是治疗甲状腺癌,尤其是放射性碘难治性分化型甲状腺癌最有希望的药物之一。
Background:Lenvatinib is a multi-target receptor tyrosine kinase inhibitor,and the US Food and Drug Administration(FDA) approved lenvatinib in 2015 for the treatment of thyroid cancer,especially local recurrence or metastatic,progressive, radioactive iodine-refractory differentiated thyroid cancer patients.And in December 2017,levabinib was granted the priority approval accreditation by the State Food and Drug Administration of China as an anti-liver cancer preparation.This article mainly discusses the current clinical research progress of levartinib in thyroid cancer. The authors searched from Pubmed,Cochrane Library,EMBASE,China National Knowledge Infrastructure Database and Wanfang Database,and then assessed the progression-free survival(PFS),objective response rate(ORR) and adverse events of lenvatinib in treatment of radioactive iodine-refractory differentiated throid cancer.Current clinical studies have shown that lenvatinib prolongs PFS in patients with radioactive iodine-refractory differentiated thyroid cancer and improves ORR High blood pressure,diarrhea,fatigued,loss of appetite,weight loss,etc. are the most common side effects.Conclusion:Lenvatinib can significantly improve PFS and ORR in patients with radioactive iodine-refractory differentiated thyroid cancer.Despite its side effects,it is still one of the most promising drugs for the treatment of thyroid cancer,especially radioactive iodine-refractory differentiated thyroid cancer.
Background:Lenvatinib is a multi-target receptor tyrosine kinase inhibitor,and the US Food and Drug Administration(FDA) approved lenvatinib in 2015 for the treatment of thyroid cancer,especially local recurrence or metastatic,progressive, radioactive iodine-refractory differentiated thyroid cancer patients.And in December 2017,levabinib was granted the priority approval accreditation by the State Food and Drug Administration of China as an anti-liver cancer preparation.This article mainly discusses the current clinical research progress of levartinib in thyroid cancer. The authors searched from Pubmed,Cochrane Library,EMBASE,China National Knowledge Infrastructure Database and Wanfang Database,and then assessed the progression-free survival(PFS),objective response rate(ORR) and adverse events of lenvatinib in treatment of radioactive iodine-refractory differentiated throid cancer.Current clinical studies have shown that lenvatinib prolongs PFS in patients with radioactive iodine-refractory differentiated thyroid cancer and improves ORR High blood pressure,diarrhea,fatigued,loss of appetite,weight loss,etc. are the most common side effects.Conclusion:Lenvatinib can significantly improve PFS and ORR in patients with radioactive iodine-refractory differentiated thyroid cancer.Despite its side effects,it is still one of the most promising drugs for the treatment of thyroid cancer,especially radioactive iodine-refractory differentiated thyroid cancer.
引文
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[19]Brose,M.S.,et al.Rationale and design of decision:a double-blind,randomized,placebo-controlled phase III trial evaluating the efficacy and safety of sorafenib in patients with locally advanced or metastatic radioactive iodine(RAI)-refractory,differentiated thyroid cancer[J].BMC Cancer,2011,11:349.
[20]Gupta-Abramson,V.,et al.Phase II trial of sorafenib in advanced thyroid cancer[J].J Clin Oncol,2008,26(29):4714-9.
[2]Cabanillas,M.E.,D.G.McFadden and C.Durante,Thyroid cancer[J].Lancet,2016,388(10061):2783-2795.
[3]Durante,C.,et al.Long-term outcome of 444 patients with distant metastases from papillary and follicular thyroid carcinoma:benefits and limits of radioiodine therapy[J].J Clin Endocrinol Metab,2006,91(8):2892-9.
[4]Jin,Y.,et al.Radioiodine refractory differentiated thyroid cancer[J].Crit Rev Oncol Hematol,2018,125:111-120.
[5]Suyama,K.and H.Iwase,Lenvatinib:A Promising Molecular Targeted Agent for Multiple Cancers[J].Cancer Control,2018,25(1):1073274818789361.
[6]Cabanillas,M.E.,et al.A phase 2 trial of lenvatinib(E7080)in advanced,progressive,radioiodine-refractory,differentiated thyroid cancer:A clinical outcomes and biomarker assessment[J].Cancer,2015,121(16):2749-56.
[7]Schlumberger,M.,et al.Lenvatinib versus placebo in radioiodine-refractory thyroid cancer[J].N Engl J Med,2015,372(7):621-30.
[8]Brose,M.S.,et al.Effect of Age on the Efficacy and Safety of Lenvatinib in Radioiodine-Refractory Differentiated Thyroid Cancer in the Phase IIISELECT Trial[J].J Clin Oncol,2017,35(23):2692-2699.
[9]Balmelli,C.,et al.Lenvatinib in Advanced Radioiodine-Refractory Thyroid Cancer-A Retrospective Analysis of the Swiss Lenvatinib Named Patient Program[J].J Cancer,2018,9(2):p.250-255.
[10]Kiyota,N.,et al.Subgroup analysis of Japanese patients in a phase 3 study of lenvatinib in radioiodine-refractory differentiated thyroid cancer[J].Cancer Sci,2015,106(12):1714-21.
[11]Eskens,F.A.and J.Verweij.The clinical toxicity profile of vascular endothelial growth factor(VEGF)and vascular endothelial growth factor receptor(VEGFR)targeting angiogenesis inhibitors;a review[J].Eur JCancer,2006,42(18):3127-39.
[12]Klastersky,J.A.Adverse events of targeted therapies[J].Curr Opin Oncol,2014,26(4):395-402.
[13]Cao,Y.,VEGF-targeted cancer therapeutics-paradoxical effects in endocrine organs[J].Nat Rev Endocrinol,2014,10(9):530-9.
[14]Alameddine,R.S.,et al.Cardiac and vascular toxicities of angiogenesis inhibitors:The other side of the coin[J].Crit Rev Oncol Hematol,2015,96(2):195-205.
[15]Ghatalia,P.,et al.Hepatotoxicity with vascular endothelial growth factor receptor tyrosine kinase inhibitors:A meta-analysis of randomized clinical trials[J].Crit Rev Oncol Hematol,2015,93(3):257-76.
[16]Robinson,B.,et al.Characterization of Tumor Size Changes Over Time From the Phase 3 Study of Lenvatinib in Thyroid Cancer[J].J Clin Endocrinol Metab,2016,101(11):4103-4109.
[17]Leboulleux,S.,et al.Vandetanib in locally advanced or metastatic differentiated thyroid cancer:a randomised,double-blind,phase 2 trial[J].Lancet Oncol,2012,13(9):897-905.
[18]Wells,S.J.,et al.Vandetanib in patients with locally advanced or metastatic medullary thyroid cancer:a randomized,double-blind phase III trial[J].J Clin Oncol,2012,30(2):134-41.
[19]Brose,M.S.,et al.Rationale and design of decision:a double-blind,randomized,placebo-controlled phase III trial evaluating the efficacy and safety of sorafenib in patients with locally advanced or metastatic radioactive iodine(RAI)-refractory,differentiated thyroid cancer[J].BMC Cancer,2011,11:349.
[20]Gupta-Abramson,V.,et al.Phase II trial of sorafenib in advanced thyroid cancer[J].J Clin Oncol,2008,26(29):4714-9.