间变性淋巴瘤激酶酪氨酸激酶抑制剂布格替尼的药理作用与临床评价
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摘要
布格替尼(brigatinib)是第2代间变性淋巴瘤激酶(ALK)酪氨酸激酶抑制剂,通过抑制ALK自身磷酸化和ALK-介导的下游信号蛋白STAT3、AKT、ERK1/2,以及S6在体外和体内的磷酸化,而表现出对4种EML4-ALK的突变体形式的体内抗肿瘤活性。对间变性淋巴瘤激酶转移性非小细胞肺癌(NSCLC)患者有显著疗效。美国食品与药品管理局于2017年4月批准布格替尼上市,本文以布格替尼为关键词进行文献检索,并对其作用机制、药动学、临床评价、用法用量、药物相互作用及安全性等进行综述。
Brigatinib is a second-generation anaplastic lymphoma kinase(ALK) tyrosine kinase inhibitor(TKI). It shows anti-tumor activity of4 kinds of EML4-ALK mutant forms by inhibiting the phosphorylation of ALK and ALK-mediated downstream signaling proteins, STAT3, AKT,ERK1/2. also by inhibiting the phosphorylation of S 6 in vitro and in vivo. It shows a significant curative effect of the anaplastic lymphoma kinase(ALK+) metastatic non-small cell lung cancer(NSCLC) patients. FDA approved brigatinib in April 2017. After literature search for brigatinib with keywords,the mechanism of action, pharmacokinetics, clinical evaluation, dosage, drug interactions, and safety of brigatinibwere reviewed
Brigatinib is a second-generation anaplastic lymphoma kinase(ALK) tyrosine kinase inhibitor(TKI). It shows anti-tumor activity of4 kinds of EML4-ALK mutant forms by inhibiting the phosphorylation of ALK and ALK-mediated downstream signaling proteins, STAT3, AKT,ERK1/2. also by inhibiting the phosphorylation of S 6 in vitro and in vivo. It shows a significant curative effect of the anaplastic lymphoma kinase(ALK+) metastatic non-small cell lung cancer(NSCLC) patients. FDA approved brigatinib in April 2017. After literature search for brigatinib with keywords,the mechanism of action, pharmacokinetics, clinical evaluation, dosage, drug interactions, and safety of brigatinibwere reviewed
引文
[1]WHO.Globocan 2012:Estimated cancer incidence.mortality and prevalence worldwide in 2012[EB/OL].(2015-07-06)[2018-04-29].http://globocan.iarc.fr/Pasges/online.aspx
[2]张绪超,陆舜,张力,等.中国间变性淋巴瘤激酶(ALK)阳性非小细胞肺癌诊疗指南[J].中华病理学杂志,2015.44(10):696-703
[3]Solomon B J,Mok T,Kim D W,et al.First-line crizotinib versus chemotherapy in ALK-positive lung cancer[J].N Engl J Med,2014,371(23):2167-2177.
[4]Jian W,Susu B,Yaoyao C,et al.A reliable and stable method for determination of brigatinib in rat plasma by UPLC-MS/MS:Application to a pharmacokinetic study[J]J Chromatogr B Analyt Technol Biomed Life Sci,2017(1068-1069):84-89
[5]FDA.Brigatinib[EB/OL].(2017-04-28)[2018-01-29].http://www.accessdata.fda.gov/drugsatfda_docs/label/2017/2087721bl.pdf
[6]Sabari J K,Santini F C,Schram A M,et al.The activity,safety,and evolving role of brigatinib in patients with ALK-rearranged non-small cell lung cancers[J].Onco Targets Ther,2017(10):1983-1992
[7]Zhang S,Anjum R,Squillace R,et al.The potent ALK inhibitor brigatinib(AP26113)overcomes mechanisms of resistance to firstand second-Generation ALK inhibitors in preclinical models[J].Clin Cancer Res,2016,22(22):5527-5538.
[8]Kim D W,Tiseo M,Ahn M J,et al.brigatinib in Patients With Crizotinib-Refractory Anaplastic Lymphoma Kinase-Positive Non-Small-Cell Lung Cancer:A Randomized,Multicenter PhaseⅡTrial[J].J Clin Oncol,2017,35(22):2490-2498
[9]Das M.Brigatinib effective in ALK-positive non-small-cell lung cancer[J].Lancet Oncol,2017,18(6):e310
[10]Gettinger S N,Bazhenova L A,Langer C J,et al.Activity and safety of brigatinib in ALK-rearranged non-small-cell lung cancer and other malignancies:a single-arm,open-label,phase 1/2 trial[J].Lancet Oncol,2016,17(12):1683-1696
[11]Rosell R,Gettinger S N,Bazhenova L A,et al.Brigatinib efficacy and safety in patients(Pts)with anaplastic lymphoma kinase(ALK)-positive(ALK+)non-small cell lung cancer(NSCLC)in a phase 1/2 trial[J].J Thorac Oncol,2016,11(Suppl.):S114
[12]Markham A.Brigatinib:First Global Approval[J].Drugs,2017,77(10):1131-1135.
[2]张绪超,陆舜,张力,等.中国间变性淋巴瘤激酶(ALK)阳性非小细胞肺癌诊疗指南[J].中华病理学杂志,2015.44(10):696-703
[3]Solomon B J,Mok T,Kim D W,et al.First-line crizotinib versus chemotherapy in ALK-positive lung cancer[J].N Engl J Med,2014,371(23):2167-2177.
[4]Jian W,Susu B,Yaoyao C,et al.A reliable and stable method for determination of brigatinib in rat plasma by UPLC-MS/MS:Application to a pharmacokinetic study[J]J Chromatogr B Analyt Technol Biomed Life Sci,2017(1068-1069):84-89
[5]FDA.Brigatinib[EB/OL].(2017-04-28)[2018-01-29].http://www.accessdata.fda.gov/drugsatfda_docs/label/2017/2087721bl.pdf
[6]Sabari J K,Santini F C,Schram A M,et al.The activity,safety,and evolving role of brigatinib in patients with ALK-rearranged non-small cell lung cancers[J].Onco Targets Ther,2017(10):1983-1992
[7]Zhang S,Anjum R,Squillace R,et al.The potent ALK inhibitor brigatinib(AP26113)overcomes mechanisms of resistance to firstand second-Generation ALK inhibitors in preclinical models[J].Clin Cancer Res,2016,22(22):5527-5538.
[8]Kim D W,Tiseo M,Ahn M J,et al.brigatinib in Patients With Crizotinib-Refractory Anaplastic Lymphoma Kinase-Positive Non-Small-Cell Lung Cancer:A Randomized,Multicenter PhaseⅡTrial[J].J Clin Oncol,2017,35(22):2490-2498
[9]Das M.Brigatinib effective in ALK-positive non-small-cell lung cancer[J].Lancet Oncol,2017,18(6):e310
[10]Gettinger S N,Bazhenova L A,Langer C J,et al.Activity and safety of brigatinib in ALK-rearranged non-small-cell lung cancer and other malignancies:a single-arm,open-label,phase 1/2 trial[J].Lancet Oncol,2016,17(12):1683-1696
[11]Rosell R,Gettinger S N,Bazhenova L A,et al.Brigatinib efficacy and safety in patients(Pts)with anaplastic lymphoma kinase(ALK)-positive(ALK+)non-small cell lung cancer(NSCLC)in a phase 1/2 trial[J].J Thorac Oncol,2016,11(Suppl.):S114
[12]Markham A.Brigatinib:First Global Approval[J].Drugs,2017,77(10):1131-1135.