非小细胞肺癌颅脑转移的靶向治疗进展
|
摘要
颅脑是非小细胞肺癌最常见的远处器官转移部位之一,发生颅脑转移的非小细胞肺癌患者预后较差。由于血脑屏障的存在,化疗对非小细胞肺癌颅脑转移灶的疗效有限。近年来,随着分子靶向治疗的发展,非小细胞肺癌颅脑转移的治疗逐渐成为肿瘤内科研究的重点,评价靶向药物治疗颅脑转移的临床研究不断涌现并取得良好的效果,本文就非小细胞肺癌颅脑转移的靶向治疗的研究进展进行综述。
Brain is one of most common metastatic sites of non-small cell lung cancer(NSCLC). Brain metastasis has a high incidence, and implied an extremely poor prognosis. The effect of chemotherapy on brain metastasis from NSCLC is poor due to the blood brain barrier(BBB). With the development of targeted therapy, treatment of brain metastasis from NSCLC has now become the research focus in medical oncology. Recently, more and more studies and trials regarding targeted agents for brain metastases treatment, with a better curative effect were reported. This article make a summary of current situation and progress for targeted therapy for NSCLS with brain metastasis.
Brain is one of most common metastatic sites of non-small cell lung cancer(NSCLC). Brain metastasis has a high incidence, and implied an extremely poor prognosis. The effect of chemotherapy on brain metastasis from NSCLC is poor due to the blood brain barrier(BBB). With the development of targeted therapy, treatment of brain metastasis from NSCLC has now become the research focus in medical oncology. Recently, more and more studies and trials regarding targeted agents for brain metastases treatment, with a better curative effect were reported. This article make a summary of current situation and progress for targeted therapy for NSCLS with brain metastasis.
引文
[1]Rodrigus P,de Brouwer P,Raaymakers E.Brain metastases and nonsmall cell lung cancer.Prognostic factors and correlation with survival after irradiation[J].Lung Cancer,2001,32(2):129-136.
[2]Fan Y,Huang Z,Fang L,et al.Chemotherapy and EGFR tyrosine kinase inhibitors for treatment of brain metastases from non-small-cell lung cancer:survival analysis in 210 patients[J].Onco Targets Ther,2013,6:1789-1803.
[3]Zimmermann S,Peters S.Present standards and future perspectives in the treatment of metastatic non-small cell lung cancer[J].Cancer Metastasis Rev,2015,34(2):173-182.
[4]Fidler IJ.The role of the organ microenvironment in brain metastasis[J].Semin Cancer Biol,2010,21(2):107-112.
[5]Wu YL,Yang J,Zhou C,et al.BRAIN:A phaseⅢtrial comparing WBI and chemotherapy with icotinib in NSCLC with brain metastases harboring EGFR mutations(CTONG 1201)[J].J Thorac Oncol,2017,12(1):S6.
[6]Ahn MJ,Kim DW,Kim TM,et al.PhaseⅠstudy of AZD3759,a CNS penetrable EGFR inhibitor,for the treatment of non-small-cell lung cancer(NSCLC)with brain metastasis(BM)and leptomeningeal metastasis(LM)[J].J Clin Oncol,2016,34(suppl):Abstr 9003.
[7]Le Rhun E,Taillibert S,Chamberlain MC.Carcinomatous meningitis:leptomeningeal metastases in solid tumors[J].Surg Neurol Int,2013,4(Suppl4):S265-S288.
[8]Li YS,Jiang BY,Yang JJ,et al.Leptomeningeal metastases in patients with NSCLC with EGFR mutations[J].J Thorac Oncol,2016,11(11):1962-1969.
[9]Yang JCH.Osimertinib activity in patients(pts)with leptomeningeal(LM)disease from non-small cell lung cancer(NSCLC):updated results from BLOOM,a Phase I study.Abstract 9002[Oral Presentation]:annual meeting of the American Society of Clinical Oncology,2016[C].
[10]Mok TS,Wu Y,Ahn MJ,et al.Osimertinib or platinum-pemetrexed in EGFR T790M-positive lung cancer[J].N Engl J Med,2017,376(7):629-640.
[11]Kang HJ,Lim HJ,Park JS,et al.Comparison of clinical characteristics between patients with ALK-positive and EGFR-positive lung adenocarcinoma[J].Respir Med,2014,108(2):388-394.
[12]Doebele RC,Lu X,Sumey C,et al.Oncogene status predicts patterns of metastatic spread in treatment-naive nonsmall cell lung cancer[J].Cancer,2011,118(18):4502-4511.
[13]刘雨桃,王子平,胡兴胜,等.克唑替尼对ALK融合基因阳性脑转移肺癌患者的疗效分析[J].中国新药杂志,2015,24(15):1760-1764.
[14]Gadgeel SM,Shaw AT,Barlesi F,et al.Cumulative incidence rates for CNS and non-CNS progression by baseline CNS metastases status using data from two alectinib phaseⅡstudies[J].2016,15(10):1990-2001.
[15]Zhou C,Wu YL,Chen G,et al.BEYOND:a randomized,doubleblind,placebo-controlled,multicenter,phaseⅢstudy of first-line carboplatin/paclitaxel plus bevacizumab or placebo in Chinese patients with advanced or recurrent nonsquamous non-small-cell lung cancer[J].J Clin Oncol,2015,33(19):2197-2204.
[16]Besse B,Moulec SL,Mazières J,et al.Bevacizumab in patients with nonsquamous non-small cell lung cancer and asymptomatic,intreated brain metastases(BRAIN):A Nonrandomized,PhaseⅡstudy[J].Clin Cancer Res,2015,21(8):1896-1903.
[17]Tang N,Guo J,Zhang Q,et al.Greater efficacy of chemotherapy plus bevacizumab compared to chemo-and targeted therapy alone on nonsmall cell lung cancer patients with brain metastasis[J].Oncotarget,2015,7(3):3635-3644.
[18]赵儒钢,孟祥颖,申戈,等.贝伐珠单抗治疗脑转移瘤难治性瘤周水肿的疗效分析[J].临床肿瘤学杂志,2016,21(3):233-237.
[19]Goldberg SB,Gettinger SN,Mahajan A,et al.Pembrolizumab for patients with melanoma or non-small-cell lung cancer and untreated brain metastases:early analysis of a non-randomised,open-label,phase 2 trial[J].Lancet Oncol,2016,17(7):976-983.
[20]Goldman JW,Crino L,Vokes EE,et al.Nivolumab(nivo)in patients(pts)with advanced(adv)NSCLC and central nervous system(CNS)metastases(mets)[J].J Thorac Oncol,2016,11(10S):S238-S239.
[21]罗鹏辉,王湘萍,莫敦昌,等.埃克替尼联合放疗治疗EGFR突变型肺腺癌无症状脑转移疗效观察[J].海南医学,2017,28(8):1219-1222.
[2]Fan Y,Huang Z,Fang L,et al.Chemotherapy and EGFR tyrosine kinase inhibitors for treatment of brain metastases from non-small-cell lung cancer:survival analysis in 210 patients[J].Onco Targets Ther,2013,6:1789-1803.
[3]Zimmermann S,Peters S.Present standards and future perspectives in the treatment of metastatic non-small cell lung cancer[J].Cancer Metastasis Rev,2015,34(2):173-182.
[4]Fidler IJ.The role of the organ microenvironment in brain metastasis[J].Semin Cancer Biol,2010,21(2):107-112.
[5]Wu YL,Yang J,Zhou C,et al.BRAIN:A phaseⅢtrial comparing WBI and chemotherapy with icotinib in NSCLC with brain metastases harboring EGFR mutations(CTONG 1201)[J].J Thorac Oncol,2017,12(1):S6.
[6]Ahn MJ,Kim DW,Kim TM,et al.PhaseⅠstudy of AZD3759,a CNS penetrable EGFR inhibitor,for the treatment of non-small-cell lung cancer(NSCLC)with brain metastasis(BM)and leptomeningeal metastasis(LM)[J].J Clin Oncol,2016,34(suppl):Abstr 9003.
[7]Le Rhun E,Taillibert S,Chamberlain MC.Carcinomatous meningitis:leptomeningeal metastases in solid tumors[J].Surg Neurol Int,2013,4(Suppl4):S265-S288.
[8]Li YS,Jiang BY,Yang JJ,et al.Leptomeningeal metastases in patients with NSCLC with EGFR mutations[J].J Thorac Oncol,2016,11(11):1962-1969.
[9]Yang JCH.Osimertinib activity in patients(pts)with leptomeningeal(LM)disease from non-small cell lung cancer(NSCLC):updated results from BLOOM,a Phase I study.Abstract 9002[Oral Presentation]:annual meeting of the American Society of Clinical Oncology,2016[C].
[10]Mok TS,Wu Y,Ahn MJ,et al.Osimertinib or platinum-pemetrexed in EGFR T790M-positive lung cancer[J].N Engl J Med,2017,376(7):629-640.
[11]Kang HJ,Lim HJ,Park JS,et al.Comparison of clinical characteristics between patients with ALK-positive and EGFR-positive lung adenocarcinoma[J].Respir Med,2014,108(2):388-394.
[12]Doebele RC,Lu X,Sumey C,et al.Oncogene status predicts patterns of metastatic spread in treatment-naive nonsmall cell lung cancer[J].Cancer,2011,118(18):4502-4511.
[13]刘雨桃,王子平,胡兴胜,等.克唑替尼对ALK融合基因阳性脑转移肺癌患者的疗效分析[J].中国新药杂志,2015,24(15):1760-1764.
[14]Gadgeel SM,Shaw AT,Barlesi F,et al.Cumulative incidence rates for CNS and non-CNS progression by baseline CNS metastases status using data from two alectinib phaseⅡstudies[J].2016,15(10):1990-2001.
[15]Zhou C,Wu YL,Chen G,et al.BEYOND:a randomized,doubleblind,placebo-controlled,multicenter,phaseⅢstudy of first-line carboplatin/paclitaxel plus bevacizumab or placebo in Chinese patients with advanced or recurrent nonsquamous non-small-cell lung cancer[J].J Clin Oncol,2015,33(19):2197-2204.
[16]Besse B,Moulec SL,Mazières J,et al.Bevacizumab in patients with nonsquamous non-small cell lung cancer and asymptomatic,intreated brain metastases(BRAIN):A Nonrandomized,PhaseⅡstudy[J].Clin Cancer Res,2015,21(8):1896-1903.
[17]Tang N,Guo J,Zhang Q,et al.Greater efficacy of chemotherapy plus bevacizumab compared to chemo-and targeted therapy alone on nonsmall cell lung cancer patients with brain metastasis[J].Oncotarget,2015,7(3):3635-3644.
[18]赵儒钢,孟祥颖,申戈,等.贝伐珠单抗治疗脑转移瘤难治性瘤周水肿的疗效分析[J].临床肿瘤学杂志,2016,21(3):233-237.
[19]Goldberg SB,Gettinger SN,Mahajan A,et al.Pembrolizumab for patients with melanoma or non-small-cell lung cancer and untreated brain metastases:early analysis of a non-randomised,open-label,phase 2 trial[J].Lancet Oncol,2016,17(7):976-983.
[20]Goldman JW,Crino L,Vokes EE,et al.Nivolumab(nivo)in patients(pts)with advanced(adv)NSCLC and central nervous system(CNS)metastases(mets)[J].J Thorac Oncol,2016,11(10S):S238-S239.
[21]罗鹏辉,王湘萍,莫敦昌,等.埃克替尼联合放疗治疗EGFR突变型肺腺癌无症状脑转移疗效观察[J].海南医学,2017,28(8):1219-1222.