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肺腺癌：修订间差异

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第27行： 第27行：
腫瘤生長有賴於活化細胞表面受體，控制細胞內[[訊息傳遞 (生物)|訊息傳遞]]，以調節細胞增長、凋亡、附著、移動與血管新生。
腫瘤生長有賴於活化細胞表面受體，控制細胞內[[訊息傳遞 (生物)|訊息傳遞]]，以調節細胞增長、凋亡、附著、移動與血管新生。


[[表皮生長因子受體]]是[[細胞膜]]上的一種[[蛋白質]]，作為[[表皮生長因子]]的接受器，表皮生長因子受體與上皮細胞癌的生長及惡化有關連性，約三分之二之各類癌症有表皮生長因子受體的表現<ref>{{Cite journal|title=EGFR exon 20 insertion mutations in non-small-cell lung cancer: preclinical data and clinical implications|url=https://linkinghub.elsevier.com/retrieve/pii/S1470204511701292|last=Yasuda|first=Hiroyuki|last2=Kobayashi|first2=Susumu|date=2012-01|journal=The Lancet Oncology|issue=1|doi=10.1016/S1470-2045(11)70129-2|volume=13|pages=e23–e31|language=en|last3=Costa|first3=Daniel B}}</ref>。表皮生長因子受體須經由[[二聚體|二聚化]]才能活化[[酪氨酸激酶]]。
[[表皮生长因子受体|表皮生長因子受體]]是[[細胞膜]]上的一種[[蛋白質]]，作為[[表皮生長因子]]的接受器，表皮生長因子受體與上皮細胞癌的生長及惡化有關連性，約三分之二之各類癌症有表皮生長因子受體的表現<ref>{{Cite journal|title=EGFR exon 20 insertion mutations in non-small-cell lung cancer: preclinical data and clinical implications|url=https://linkinghub.elsevier.com/retrieve/pii/S1470204511701292|last=Yasuda|first=Hiroyuki|last2=Kobayashi|first2=Susumu|date=2012-01|journal=The Lancet Oncology|issue=1|doi=10.1016/S1470-2045(11)70129-2|volume=13|pages=e23–e31|language=en|last3=Costa|first3=Daniel B}}</ref>。表皮生長因子受體須經由[[二聚體|二聚化]]才能活化[[酪氨酸激酶]]。


肺腺癌細胞若有表皮生長因子受體[[突變]]，則對表皮生長因子受體-[[酪氨酸激酶抑制劑]]具高敏感性，突變與否可做為其是否有效的預測因子。歐美地區肺腺癌的病患約15%具表皮生長因子受體突變，[[亞洲]]地區約50-60%，多發生於女性與非吸菸者<ref>{{Cite journal|title=Role of K-ras gene mutations in carcinogenesis, diagnosis and treatment of patients with lung adenocarcinoma|url=http://dx.doi.org/10.3724/sp.j.1008.2011.00545|last=WANG|first=Bin|last2=HAN|first2=Yi-ping|date=2011-06-29|journal=Academic Journal of Second Military Medical University|issue=5|doi=10.3724/sp.j.1008.2011.00545|volume=31|pages=545–549|issn=0258-879X}}</ref>。
肺腺癌細胞若有表皮生長因子受體[[突變]]，則對表皮生長因子受體-[[酪氨酸激酶抑制劑]]具高敏感性，突變與否可做為其是否有效的預測因子。歐美地區肺腺癌的病患約15%具表皮生長因子受體突變，[[亞洲]]地區約50-60%，多發生於女性與非吸菸者<ref>{{Cite journal|title=Role of K-ras gene mutations in carcinogenesis, diagnosis and treatment of patients with lung adenocarcinoma|url=http://dx.doi.org/10.3724/sp.j.1008.2011.00545|last=WANG|first=Bin|last2=HAN|first2=Yi-ping|date=2011-06-29|journal=Academic Journal of Second Military Medical University|issue=5|doi=10.3724/sp.j.1008.2011.00545|volume=31|pages=545–549|issn=0258-879X}}</ref>。
第35行： 第35行：
[[阿法替尼]]為第二代不可逆酪氨酸激酶抑制劑，在[[美國]]、[[歐洲]]和[[台灣]]批准作為一線治療藥物<ref>{{Cite journal|title=Afatinib: First Global Approval|url=http://dx.doi.org/10.1007/s40265-013-0111-6|last=Dungo|first=Rosselle T.|last2=Keating|first2=Gillian M.|date=2013-08-28|journal=Drugs|issue=13|doi=10.1007/s40265-013-0111-6|volume=73|pages=1503–1515|issn=0012-6667}}</ref>。以亞洲病患為對象的試驗中，針對表皮生長因子受體突變的肺腺癌，與化療藥物[[吉西他濱]]和[[順鉑]]比較，酪氨酸激酶抑制劑可延長疾病無惡化存活期<ref>{{Cite journal|title=Afatinib versus cisplatin-based chemotherapy for EGFR mutation-positive lung adenocarcinoma (LUX-Lung 3 and LUX-Lung 6): analysis of overall survival data from two randomised, phase 3 trials|url=http://dx.doi.org/10.1016/s1470-2045(14)71173-8|last=Yang|first=James Chih-Hsin|last2=Wu|first2=Yi-Long|date=2015-02|journal=The Lancet Oncology|issue=2|doi=10.1016/s1470-2045(14)71173-8|volume=16|pages=141–151|issn=1470-2045|last3=Schuler|first3=Martin|last4=Sebastian|first4=Martin|last5=Popat|first5=Sanjay|last6=Yamamoto|first6=Nobuyuki|last7=Zhou|first7=Caicun|last8=Hu|first8=Cheng-Ping|last9=O'Byrne|first9=Kenneth}}</ref>。
[[阿法替尼]]為第二代不可逆酪氨酸激酶抑制劑，在[[美國]]、[[歐洲]]和[[台灣]]批准作為一線治療藥物<ref>{{Cite journal|title=Afatinib: First Global Approval|url=http://dx.doi.org/10.1007/s40265-013-0111-6|last=Dungo|first=Rosselle T.|last2=Keating|first2=Gillian M.|date=2013-08-28|journal=Drugs|issue=13|doi=10.1007/s40265-013-0111-6|volume=73|pages=1503–1515|issn=0012-6667}}</ref>。以亞洲病患為對象的試驗中，針對表皮生長因子受體突變的肺腺癌，與化療藥物[[吉西他濱]]和[[順鉑]]比較，酪氨酸激酶抑制劑可延長疾病無惡化存活期<ref>{{Cite journal|title=Afatinib versus cisplatin-based chemotherapy for EGFR mutation-positive lung adenocarcinoma (LUX-Lung 3 and LUX-Lung 6): analysis of overall survival data from two randomised, phase 3 trials|url=http://dx.doi.org/10.1016/s1470-2045(14)71173-8|last=Yang|first=James Chih-Hsin|last2=Wu|first2=Yi-Long|date=2015-02|journal=The Lancet Oncology|issue=2|doi=10.1016/s1470-2045(14)71173-8|volume=16|pages=141–151|issn=1470-2045|last3=Schuler|first3=Martin|last4=Sebastian|first4=Martin|last5=Popat|first5=Sanjay|last6=Yamamoto|first6=Nobuyuki|last7=Zhou|first7=Caicun|last8=Hu|first8=Cheng-Ping|last9=O'Byrne|first9=Kenneth}}</ref>。


{{Le|美國臨床腫瘤醫學會|American Society of Clinical Oncology}}官方年會發表的數據顯示阿法替尼的疾病無惡化存活期是11個月，化療為5.6個月。47%病例於療程一年後病情無惡化，接受化療的病患為2%<ref>{{Cite journal|title=A phase I dose escalation study of BIBW 2992, an irreversible dual EGFR/HER2 receptor tyrosine kinase inhibitor, in a continuous schedule in patients with advanced solid tumours|url=http://dx.doi.org/10.1200/jco.2006.24.18_suppl.2074|last=Agus|first=D. B.|last2=Terlizzi|first2=E.|date=2006-06-20|journal=Journal of Clinical Oncology|issue=18_suppl|doi=10.1200/jco.2006.24.18_suppl.2074|volume=24|pages=2074–2074|issn=0732-183X|last3=Stopfer|first3=P.|last4=Amelsberg|first4=A.|last5=Gordon|first5=M. S.}}</ref>。
{{Le|美國臨床腫瘤醫學會|American Society of Clinical Oncology}}官方年會發表的數據顯示[[阿法替尼]]的疾病無惡化存活期是11個月，化療為5.6個月。47%病例於療程一年後病情無惡化，接受化療的病患為2%<ref>{{Cite journal|title=A phase I dose escalation study of BIBW 2992, an irreversible dual EGFR/HER2 receptor tyrosine kinase inhibitor, in a continuous schedule in patients with advanced solid tumours|url=http://dx.doi.org/10.1200/jco.2006.24.18_suppl.2074|last=Agus|first=D. B.|last2=Terlizzi|first2=E.|date=2006-06-20|journal=Journal of Clinical Oncology|issue=18_suppl|doi=10.1200/jco.2006.24.18_suppl.2074|volume=24|pages=2074–2074|issn=0732-183X|last3=Stopfer|first3=P.|last4=Amelsberg|first4=A.|last5=Gordon|first5=M. S.}}</ref>。

另外，新研究指出，[[阿法替尼]]與其他標靶藥物[[吉非替尼]]相比，藥物治療到失效的中位數，[[阿法替尼]]為13.7個月、[[吉非替尼]]為11.5個月。<ref>{{Cite journal|title=Afatinib versus gefitinib as first-line treatment of patients with EGFR mutation-positive non-small-cell lung cancer (LUX-Lung 7): a phase 2B, open-label, randomised controlled trial|url=https://linkinghub.elsevier.com/retrieve/pii/S147020451630033X|last=Park|first=Keunchil|last2=Tan|first2=Eng-Huat|date=2016-05|journal=The Lancet Oncology|issue=5|doi=10.1016/S1470-2045(16)30033-X|volume=17|pages=577–589|language=en|last3=O'Byrne|first3=Ken|last4=Zhang|first4=Li|last5=Boyer|first5=Michael|last6=Mok|first6=Tony|last7=Hirsh|first7=Vera|last8=Yang|first8=James Chih-Hsin|last9=Lee|first9=Ki Hyeong}}</ref>

臨床研究顯示，[[表皮生长因子受体|表皮生長因子受體]]之標靶藥物應於第一線開始使用，若確定有T790M突變，則使用相對應的標靶藥物。隨機對照試驗表明，在非小細胞癌有表皮生長因子受體突變的患者中，[[阿法替尼]]和[[奥希替尼|奧希替尼]]在一線治療中優於第一代酪氨酸激酶抑制劑，此外，[[奥希替尼|奧希替尼]]可改善第一線治療後產生T790M突變的患者的惡化存活期。<ref>{{Cite journal|title=Sequential treatment with afatinib and osimertinib in patients with EGFR mutation-positive non-small-cell lung cancer: an observational study|url=https://www.futuremedicine.com/doi/10.2217/fon-2018-0711|last=Hochmair|first=Maximilian J|last2=Morabito|first2=Alessandro|date=2018-11|journal=Future Oncology|issue=27|doi=10.2217/fon-2018-0711|volume=14|pages=2861–2874|language=en|issn=1479-6694|last3=Hao|first3=Desiree|last4=Yang|first4=Cheng-Ta|last5=Soo|first5=Ross A|last6=Yang|first6=James C-H|last7=Gucalp|first7=Rasim|last8=Halmos|first8=Balazs|last9=Wang|first9=Lara}}</ref>
{| class="wikitable"
|'''標靶藥物'''
|'''療效'''
|'''常見副作用'''
|-
| colspan="3" |[[表皮生长因子受体|表皮生長因子受體]]'''突變'''
|-
|'''[[阿法替尼]]'''
|(第一線)

腫瘤反應率約7成<ref>{{Cite journal|title=LUX-Lung 7: is there enough data for a final conclusion? – Author's reply|url=http://dx.doi.org/10.1016/s1470-2045(16)30244-3|last=Park|first=Keunchil|date=2016-07|journal=The Lancet Oncology|issue=7|doi=10.1016/s1470-2045(16)30244-3|volume=17|pages=e268–e269|issn=1470-2045}}</ref>

無疾病惡化存活期中位數11-13.6個月<ref>{{Cite journal|title=LUX-Lung 7: is there enough data for a final conclusion? – Author's reply|url=http://dx.doi.org/10.1016/s1470-2045(16)30244-3|last=Park|first=Keunchil|date=2016-07|journal=The Lancet Oncology|issue=7|doi=10.1016/s1470-2045(16)30244-3|volume=17|pages=e268–e269|issn=1470-2045}}</ref><ref>{{Cite journal|title=EGFR TKI as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer|url=http://www.oncotarget.com/fulltext/20095|last=Nan|first=Xueli|last2=Xie|first2=Chao|date=2017-09-26|journal=Oncotarget|issue=43|doi=10.18632/oncotarget.20095|volume=8|language=en|issn=1949-2553|last3=Yu|first3=Xueyan|last4=Liu|first4=Jie}}</ref>
|腹瀉、甲溝炎、皮疹
|-
|'''厄洛替尼'''
|(第一線)

腫瘤反應率約6-7成<ref>{{Cite journal|title=Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial|url=https://linkinghub.elsevier.com/retrieve/pii/S147020451170393X|last=Rosell|first=Rafael|last2=Carcereny|first2=Enric|date=2012-03|journal=The Lancet Oncology|issue=3|doi=10.1016/S1470-2045(11)70393-X|volume=13|pages=239–246|language=en|last3=Gervais|first3=Radj|last4=Vergnenegre|first4=Alain|last5=Massuti|first5=Bartomeu|last6=Felip|first6=Enriqueta|last7=Palmero|first7=Ramon|last8=Garcia-Gomez|first8=Ramon|last9=Pallares|first9=Cinta}}</ref>

無疾病惡化存活期中位數9.7-13.1個月<ref>{{Cite journal|title=EGFR TKI as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer|url=http://www.oncotarget.com/fulltext/20095|last=Nan|first=Xueli|last2=Xie|first2=Chao|date=2017-09-26|journal=Oncotarget|issue=43|doi=10.18632/oncotarget.20095|volume=8|language=en|issn=1949-2553|last3=Yu|first3=Xueyan|last4=Liu|first4=Jie}}</ref><ref>{{Cite journal|title=Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial|url=https://linkinghub.elsevier.com/retrieve/pii/S147020451170393X|last=Rosell|first=Rafael|last2=Carcereny|first2=Enric|date=2012-03|journal=The Lancet Oncology|issue=3|doi=10.1016/S1470-2045(11)70393-X|volume=13|pages=239–246|language=en|last3=Gervais|first3=Radj|last4=Vergnenegre|first4=Alain|last5=Massuti|first5=Bartomeu|last6=Felip|first6=Enriqueta|last7=Palmero|first7=Ramon|last8=Garcia-Gomez|first8=Ramon|last9=Pallares|first9=Cinta}}</ref>
|皮疹、腹瀉、噁心、食慾下降、呼吸困難、肝功能損傷
|-
|[[吉非替尼|'''吉非替尼''']]
|(第一線)

腫瘤反應率約6-7成<ref>{{Cite journal|title=Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial|url=https://linkinghub.elsevier.com/retrieve/pii/S147020451170393X|last=Rosell|first=Rafael|last2=Carcereny|first2=Enric|date=2012-03|journal=The Lancet Oncology|issue=3|doi=10.1016/S1470-2045(11)70393-X|volume=13|pages=239–246|language=en|last3=Gervais|first3=Radj|last4=Vergnenegre|first4=Alain|last5=Massuti|first5=Bartomeu|last6=Felip|first6=Enriqueta|last7=Palmero|first7=Ramon|last8=Garcia-Gomez|first8=Ramon|last9=Pallares|first9=Cinta}}</ref>

無疾病惡化存活期中位數9.2-10.9個月<ref>{{Cite journal|title=EGFR TKI as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer|url=http://www.oncotarget.com/fulltext/20095|last=Nan|first=Xueli|last2=Xie|first2=Chao|date=2017-09-26|journal=Oncotarget|issue=43|doi=10.18632/oncotarget.20095|volume=8|language=en|issn=1949-2553|last3=Yu|first3=Xueyan|last4=Liu|first4=Jie}}</ref><ref>{{Cite journal|title=Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial|url=https://linkinghub.elsevier.com/retrieve/pii/S147020451170393X|last=Rosell|first=Rafael|last2=Carcereny|first2=Enric|date=2012-03|journal=The Lancet Oncology|issue=3|doi=10.1016/S1470-2045(11)70393-X|volume=13|pages=239–246|language=en|last3=Gervais|first3=Radj|last4=Vergnenegre|first4=Alain|last5=Massuti|first5=Bartomeu|last6=Felip|first6=Enriqueta|last7=Palmero|first7=Ramon|last8=Garcia-Gomez|first8=Ramon|last9=Pallares|first9=Cinta}}</ref>
|肝膽功能異常、腹瀉、噁心、皮膚乾燥、間質性肺病
|-
|[[奥希替尼|'''奧希替尼''']]
|(第一線)

腫瘤反應率約7成<ref>{{Cite journal|title=LUX-Lung 7: is there enough data for a final conclusion? – Author's reply|url=http://dx.doi.org/10.1016/s1470-2045(16)30244-3|last=Park|first=Keunchil|date=2016-07|journal=The Lancet Oncology|issue=7|doi=10.1016/s1470-2045(16)30244-3|volume=17|pages=e268–e269|issn=1470-2045}}</ref><ref>{{Cite journal|title=EGFR TKI as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer|url=http://www.oncotarget.com/fulltext/20095|last=Nan|first=Xueli|last2=Xie|first2=Chao|date=2017-09-26|journal=Oncotarget|issue=43|doi=10.18632/oncotarget.20095|volume=8|language=en|issn=1949-2553|last3=Yu|first3=Xueyan|last4=Liu|first4=Jie}}</ref>

無疾病惡化存活期中位數16.5-18.9個月<ref>{{Cite journal|title=Expression of Concern: Beltrami AP et al. Evidence That Human Cardiac Myocytes Divide after Myocardial Infarction. N Engl J Med 2001;344:1750-7 and Quaini F et al. Chimerism of the Transplanted Heart. N Engl J Med 2002;346:5-15.|url=http://dx.doi.org/10.1056/nejme1813801|last=Drazen|first=Jeffrey M.|date=2018-11-08|journal=New England Journal of Medicine|issue=19|doi=10.1056/nejme1813801|volume=379|pages=1870–1870|issn=0028-4793}}</ref><ref>{{Cite journal|title=Osimertinib versus Standard of Care EGFR TKI as First-Line Treatment in Patients with EGFRm Advanced NSCLC: FLAURA Asian Subset|url=https://linkinghub.elsevier.com/retrieve/pii/S1556086418330910|last=Cho|first=Byoung Chul|last2=Chewaskulyong|first2=Busayamas|date=2019-01|journal=Journal of Thoracic Oncology|issue=1|doi=10.1016/j.jtho.2018.09.004|volume=14|pages=99–106|language=en|last3=Lee|first3=Ki Hyeong|last4=Dechaphunkul|first4=Arunee|last5=Sriuranpong|first5=Virote|last6=Imamura|first6=Fumio|last7=Nogami|first7=Naoyuki|last8=Kurata|first8=Takayasu|last9=Okamoto|first9=Isamu}}</ref>
|間質性肺病、腹瀉、便秘、皮膚疹、噁心嘔吐、皮膚乾癢、甲溝炎、咳嗽
|}
非小細胞肺癌中約有5%左右的患者帶有{{Le|間變性淋巴瘤激酶|Anaplastic lymphoma kinase}}基因突變<ref>{{Cite journal|title=Identification of the transforming EML4–ALK fusion gene in non-small-cell lung cancer|url=http://www.nature.com/articles/nature05945|last=Soda|first=Manabu|last2=Choi|first2=Young Lim|date=2007-08|journal=Nature|issue=7153|doi=10.1038/nature05945|volume=448|pages=561–566|language=en|issn=0028-0836|last3=Enomoto|first3=Munehiro|last4=Takada|first4=Shuji|last5=Yamashita|first5=Yoshihiro|last6=Ishikawa|first6=Shunpei|last7=Fujiwara|first7=Shin-ichiro|last8=Watanabe|first8=Hideki|last9=Kurashina|first9=Kentaro}}</ref>，平均52歲發病，相對於其他肺癌患者平均68歲，較為年輕，不抽菸或輕度抽菸。{{Le|間變性淋巴瘤激酶|Anaplastic lymphoma kinase}}基因最初是被發現在部分異生性大細胞淋巴瘤，因此被稱為{{Le|間變性淋巴瘤激酶|Anaplastic lymphoma kinase}}，間變性淋巴瘤激酶在正常情況下是處於休眠狀態, 但是如果發生斷裂錯位, 和另一個基因EML4融合成突變的EML-4-ALK 致癌基因，此形態的基因突變會激活{{Le|間變性淋巴瘤激酶|Anaplastic lymphoma kinase}}融合蛋白，並活化下游多條細胞訊息傳遞路徑，驅動細胞發生癌變。<ref>{{Cite journal|title=Diagnosis and Treatment of Anaplastic Lymphoma Kinase–Positive Non–Small Cell Lung Cancer|url=https://linkinghub.elsevier.com/retrieve/pii/S0889858816301265|last=Arbour|first=Kathryn C.|last2=Riely|first2=Gregory J.|date=2017-02|journal=Hematology/Oncology Clinics of North America|issue=1|doi=10.1016/j.hoc.2016.08.012|volume=31|pages=101–111|language=en|pmc=PMC5154547|pmid=27912826}}</ref>
{| class="wikitable"
|'''標靶藥物'''
|'''療效'''
|'''常見副作用'''
|-
| colspan="3" |{{Le|間變性淋巴瘤激酶|Anaplastic lymphoma kinase}}'''基因突變'''
|-
|'''艾樂替尼'''
|(第一線)

腫瘤反應率7-8成<ref>{{Cite journal|title=FDA Approves Alecensa (Alectinib) for ALK-Pos NSCLC|url=http://dx.doi.org/10.1097/01.cot.0000479770.87086.66|date=2016-01|journal=Oncology Times|issue=1|doi=10.1097/01.cot.0000479770.87086.66|volume=38|pages=37|issn=0276-2234}}</ref>

無疾病惡化存活期中位數25個月 <ref>{{Cite web|url=https://info.fda.gov.tw/MLMS/H0001D.aspx?Type=Lic&LicId=52027028|accessdate=2020-04-01|work=info.fda.gov.tw}}</ref>
|腸胃道不良反應、疲倦、肌痛、心搏徐緩、腎功能異常
|-
|'''色瑞替尼'''
|(第一線)

腫瘤反應率7成<ref>{{Cite web|url=https://info.fda.gov.tw/MLMS/H0001D.aspx?Type=Lic&LicId=52026674|accessdate=2020-04-01|work=info.fda.gov.tw}}</ref>

無疾病惡化存活期中位數16.6個月 <ref>{{Cite journal|title=First-line ceritinib versus platinum-based chemotherapy in advanced ALK -rearranged non-small-cell lung cancer (ASCEND-4): a randomised, open-label, phase 3 study|url=https://linkinghub.elsevier.com/retrieve/pii/S014067361730123X|last=Soria|first=Jean-Charles|last2=Tan|first2=Daniel S W|date=2017-03|journal=The Lancet|issue=10072|doi=10.1016/S0140-6736(17)30123-X|volume=389|pages=917–929|language=en|last3=Chiari|first3=Rita|last4=Wu|first4=Yi-Long|last5=Paz-Ares|first5=Luis|last6=Wolf|first6=Juergen|last7=Geater|first7=Sarayut L|last8=Orlov|first8=Sergey|last9=Cortinovis|first9=Diego}}</ref>
|肝臟毒性、間質性肺病/肺炎、腸胃道不良反應、高血糖症、脂肪酶或澱粉酶增加、心搏過慢
|-
|'''克唑替尼'''
|(第一線)

腫瘤反應率約7成<ref>{{Cite journal|title=Is there a benefit of first- or second-line crizotinib in locally advanced or metastatic anaplastic lymphoma kinase-positive non-small cell lung cancer? a meta-analysis|url=http://www.oncotarget.com/fulltext/13191|last=Hu|first=Hao|last2=Lin|first2=Wei Qing|date=2016-12-06|journal=Oncotarget|issue=49|doi=10.18632/oncotarget.13191|volume=7|language=en|issn=1949-2553|pmc=PMC5348378|pmid=27835601|last3=Zhu|first3=Qian|last4=Yang|first4=Xiong Wen|last5=Wang|first5=Hai Dong|last6=Kuang|first6=Yu Kang}}</ref>

無疾病惡化存活期中位數13.6個月[H6]
|肝毒性、肺部發炎、視覺影響、周邊水腫
|}
{{Le|原癌基因酪氨酸蛋白激酶|ROS1}}是一種關鍵的跨膜受體蛋白酪氨酸激酶，具有調節細胞凋亡、生存、分化、增殖、遷移和轉化的功能。越來越多的證據表明，在很多惡性腫瘤，包括膠質母細胞瘤、結直腸癌、胃癌、炎症性肌纖維母細胞瘤、卵巢癌、血管肉瘤和非小細胞肺癌中，{{Le|原癌基因酪氨酸蛋白激酶|ROS1}}都起到重要的作用。{{Le|原癌基因酪氨酸蛋白激酶|ROS1}}基因突變是非小細胞肺癌亞型，其發生率約佔非小細胞肺癌的1%-2%，好發於年輕、不吸煙的肺腺癌患者，這些臨床特徵與{{Le|間變性淋巴瘤激酶|Anaplastic lymphoma kinase}}基因突變的非小細胞肺癌患者類似。
{| class="wikitable"
|'''標靶藥物'''
|'''療效'''
|'''常見副作用'''
|-
| colspan="3" |{{Le|原癌基因酪氨酸蛋白激酶|ROS1}}'''基因突變'''
|-
|'''克唑替尼'''
|(第一線)

腫瘤反應率約7成 <ref>{{Cite journal|title=Recent Advances in Targeting ROS1 in Lung Cancer|url=https://linkinghub.elsevier.com/retrieve/pii/S1556086417306688|last=Lin|first=Jessica J.|last2=Shaw|first2=Alice T.|date=2017-11|journal=Journal of Thoracic Oncology|issue=11|doi=10.1016/j.jtho.2017.08.002|volume=12|pages=1611–1625|language=en|pmc=PMC5659942|pmid=28818606}}</ref>

無疾病惡化存活期中位數13.6個月<ref>{{Cite web|title=Crizotinib presented with promising efficacy but for concomitant mutation in next-generation sequencing-identified ROS1-rearranged non-small-cell lung cancer|url=https://www.dovepress.com/crizotinib-presented-with-promising-efficacy-but-for-concomitant-mutat-peer-reviewed-article-OTT|accessdate=2020-04-01|date=2018-10-15|last=Zeng|first=Liang|work=OncoTargets and Therapy|language=English}}</ref>
|肝毒性、肺部發炎、視覺影響、周邊水腫
|}


== 參見 ==
== 參見 ==

* [[小細胞癌|小細胞肺癌]]
* [[小細胞癌|小細胞肺癌]]
*[[肺結核]]
*[[肺結核]]

2020年4月1日 (三) 05:20的版本

维基百科中的醫學内容仅供参考，並不能視作專業意見。如需獲取醫療幫助或意見，请咨询专业人士。詳見醫學聲明。
各別肺癌種類比例圖，各別肺癌中抽煙與不抽煙的比例。

肺腺癌（英語：lung adenocarcinoma）是肺癌的一種，屬於非小細胞肺癌（英语：Non-small-cell lung carcinoma）。不同於鱗狀細胞肺癌（英语：Squamous-cell carcinoma of the lung），肺腺癌較容易發生於年輕女性、有抽煙史、亞洲族群。在肺部的位置常較週邊，腫瘤擴大的速度較慢（倍增時間約120天）。早期無徵兆，通常診斷出來時已經是晚期。

分化差肺腺癌。

治療

肺癌的治療是依據癌症分期、能否切除（英語：Resectability）、病患表現狀態（英语：Performance status）、腫瘤的組織學和基因組變異來做決定[1]。

手術

早期（第I、II、IIIA期）以治癒為目標，如果影像檢查和切片檢查確認可以切除，且病患能耐受手術，可採肺切除術（英语：Pneumonectomy）或肺葉切除術（英语：Lobectomy）[2]。常會使用影像輔助胸腔鏡手術（英语：Video-assisted thoracoscopic surgery）[1]。術後視病理分期給予輔助性化療或放療（英语：Adjuvant therapy）。

晚期（第IIIB、Ⅳ期）少數單一轉移病患也許可以接受手術切除或根治性放射治療[3]。緩和醫療目標在於延長生命、維持生活品質與減少治療的副作用。

化學治療

晚期與無法接除之腫瘤，第一線治療為含鉑劑合併化學治療，不建議施打超過6個療程，因雖然可延長疾病無惡化存活期（英语：Progression-free survival），但對整體存活率（英语：Survival_rate#Overall_survival）並無助益，且增加化療毒性[4]。

與鉑劑併用的第三代化學治療藥物包括吉西他濱、Taxane（英语：Taxane）、Vinorelbine（英语：Vinorelbine）、Pemetrexed（英语：Pemetrexed）、愛萊諾迪肯，並無研究顯示何者的效果優於同儕。但併用鉑劑的合併治療較單一藥物更具療效 [5]。

血管內皮生長因子廣泛存在於各種腫瘤，與其受體作用可導致血管新生，進一步造成腫瘤的成長與轉移，非小細胞肺癌（英语：Non-small-cell lung carcinoma）中血管內皮生長因子表現高者預後較差[6]。

標靶治療

帶有某些分子特性的肺腺癌可採用標靶治療。

腫瘤生長有賴於活化細胞表面受體，控制細胞內訊息傳遞，以調節細胞增長、凋亡、附著、移動與血管新生。

表皮生長因子受體是細胞膜上的一種蛋白質，作為表皮生長因子的接受器，表皮生長因子受體與上皮細胞癌的生長及惡化有關連性，約三分之二之各類癌症有表皮生長因子受體的表現[7]。表皮生長因子受體須經由二聚化才能活化酪氨酸激酶。

肺腺癌細胞若有表皮生長因子受體突變，則對表皮生長因子受體-酪氨酸激酶抑制劑具高敏感性，突變與否可做為其是否有效的預測因子。歐美地區肺腺癌的病患約15%具表皮生長因子受體突變，亞洲地區約50-60%，多發生於女性與非吸菸者[8]。

酪氨酸激酶抑制劑對於具表皮生長因子受體突變的肺腺癌患者，與傳統含鉑化療做比較，可延長疾病無惡化存活期（英语：Progression-free survival）[9]。

阿法替尼為第二代不可逆酪氨酸激酶抑制劑，在美國、歐洲和台灣批准作為一線治療藥物[10]。以亞洲病患為對象的試驗中，針對表皮生長因子受體突變的肺腺癌，與化療藥物吉西他濱和順鉑比較，酪氨酸激酶抑制劑可延長疾病無惡化存活期[11]。

美國臨床腫瘤醫學會官方年會發表的數據顯示阿法替尼的疾病無惡化存活期是11個月，化療為5.6個月。47%病例於療程一年後病情無惡化，接受化療的病患為2%[12]。

另外，新研究指出，阿法替尼與其他標靶藥物吉非替尼相比，藥物治療到失效的中位數，阿法替尼為13.7個月、吉非替尼為11.5個月。[13]

臨床研究顯示，表皮生長因子受體之標靶藥物應於第一線開始使用，若確定有T790M突變，則使用相對應的標靶藥物。隨機對照試驗表明，在非小細胞癌有表皮生長因子受體突變的患者中，阿法替尼和奧希替尼在一線治療中優於第一代酪氨酸激酶抑制劑，此外，奧希替尼可改善第一線治療後產生T790M突變的患者的惡化存活期。[14]

標靶藥物 療效 常見副作用
表皮生長因子受體突變
阿法替尼 (第一線)

腫瘤反應率約7成[15]

無疾病惡化存活期中位數11-13.6個月[16][17]

腹瀉、甲溝炎、皮疹
厄洛替尼 (第一線)

腫瘤反應率約6-7成[18]

無疾病惡化存活期中位數9.7-13.1個月[19][20]

皮疹、腹瀉、噁心、食慾下降、呼吸困難、肝功能損傷
吉非替尼 (第一線)

腫瘤反應率約6-7成[21]

無疾病惡化存活期中位數9.2-10.9個月[22][23]

肝膽功能異常、腹瀉、噁心、皮膚乾燥、間質性肺病
奧希替尼 (第一線)

腫瘤反應率約7成[24][25]

無疾病惡化存活期中位數16.5-18.9個月[26][27]

間質性肺病、腹瀉、便秘、皮膚疹、噁心嘔吐、皮膚乾癢、甲溝炎、咳嗽

非小細胞肺癌中約有5%左右的患者帶有間變性淋巴瘤激酶（英语：Anaplastic lymphoma kinase）基因突變[28]，平均52歲發病，相對於其他肺癌患者平均68歲，較為年輕，不抽菸或輕度抽菸。間變性淋巴瘤激酶（英语：Anaplastic lymphoma kinase）基因最初是被發現在部分異生性大細胞淋巴瘤，因此被稱為間變性淋巴瘤激酶（英语：Anaplastic lymphoma kinase），間變性淋巴瘤激酶在正常情況下是處於休眠狀態, 但是如果發生斷裂錯位, 和另一個基因EML4融合成突變的EML-4-ALK 致癌基因，此形態的基因突變會激活間變性淋巴瘤激酶（英语：Anaplastic lymphoma kinase）融合蛋白，並活化下游多條細胞訊息傳遞路徑，驅動細胞發生癌變。[29]

標靶藥物 療效 常見副作用
間變性淋巴瘤激酶（英语：Anaplastic lymphoma kinase）基因突變
艾樂替尼 (第一線)

腫瘤反應率7-8成[30]

無疾病惡化存活期中位數25個月 [31]

腸胃道不良反應、疲倦、肌痛、心搏徐緩、腎功能異常
色瑞替尼 (第一線)

腫瘤反應率7成[32]

無疾病惡化存活期中位數16.6個月 [33]

肝臟毒性、間質性肺病/肺炎、腸胃道不良反應、高血糖症、脂肪酶或澱粉酶增加、心搏過慢
克唑替尼 (第一線)

腫瘤反應率約7成[34]

無疾病惡化存活期中位數13.6個月[H6]

肝毒性、肺部發炎、視覺影響、周邊水腫

原癌基因酪氨酸蛋白激酶（英语：ROS1）是一種關鍵的跨膜受體蛋白酪氨酸激酶，具有調節細胞凋亡、生存、分化、增殖、遷移和轉化的功能。越來越多的證據表明，在很多惡性腫瘤，包括膠質母細胞瘤、結直腸癌、胃癌、炎症性肌纖維母細胞瘤、卵巢癌、血管肉瘤和非小細胞肺癌中，原癌基因酪氨酸蛋白激酶（英语：ROS1）都起到重要的作用。原癌基因酪氨酸蛋白激酶（英语：ROS1）基因突變是非小細胞肺癌亞型，其發生率約佔非小細胞肺癌的1%-2%，好發於年輕、不吸煙的肺腺癌患者，這些臨床特徵與間變性淋巴瘤激酶（英语：Anaplastic lymphoma kinase）基因突變的非小細胞肺癌患者類似。

標靶藥物 療效 常見副作用
原癌基因酪氨酸蛋白激酶（英语：ROS1）基因突變
克唑替尼 (第一線)

腫瘤反應率約7成 [35]

無疾病惡化存活期中位數13.6個月[36]

肝毒性、肺部發炎、視覺影響、周邊水腫

參見

參考文獻

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外部連結

上呼吸道
下呼吸道
氣管
肺
非小细胞肺癌（英语：Non-small-cell lung carcinoma）
小细胞癌
非癌
按位置
胸膜腔
取自“https://zh.wikipedia.org/w/index.php?title=肺腺癌&oldid=58914171”