<div><strong>Evidence for Disease Control with Erlotinib after Gefitinib<br/>Failure in Typical Gefitinib-Sensitive Asian Patients with Non-small<br/>Cell Lung Cancer.</strong><br/>  <br/><br/><br/>  <p class="ptArticleTOCSection"><strong>Original Article</strong><br/>  </p> Journal of Thoracic Oncology.    3(4):400-404, April 2008.<br/><br/>   <em><br/>Wong, Alvin S. MD *; Soong, Richie PhD +++; Seah, Serena Bee-Kee BSc +;<br/>Lim, Siew-Woon MSc [S]; Chuah, Khoon-Leong MD ||; Nga, Min-En MD ++;<br/>Chin, Tan-Min MD *; Soo, Ross A. MD * </em></div><p><strong> Abstract:</strong><br/>  <br/><br/>Introduction: The epidermal growth factor receptor (EGFR) tyrosine<br/>kinase inhibitors (TKIs) gefitinib and erlotinib are gaining an<br/>increasing role in the management of advanced non-small cell lung<br/>cancer (NSCLC). There is mounting interest in the benefit of<br/>administering a second TKI after failure of the first TKI, especially<br/>in Asian patients, in whom they are expected to be more efficacious.</p><p>Methods:<br/>We did a retrospective analysis of patients receiving both gefitinib<br/>and erlotinib in our institution during a 2-year period. Patients were<br/>to have received the second TKI after progressive disease on the first<br/>TKI. EGFR gene mutation analysis was done on patient tumor samples.</p><p>Results:<br/>Fourteen patients were included in the analysis, all of whom received<br/>erlotinib after progression on gefitinib. Chinese race, females,<br/>never-smokers, and adenocarcinoma subtype were predominant in their<br/>respective categories. Disease control rate was 64.3% (9 of 14) for<br/>gefitinib. Disease control rate for erlotinib administered after<br/>progression on gefitinib was 35.7% (5 of 14). All patients who achieved<br/>disease control with erlotinib after progression on gefitinib were<br/>never-smokers with adenocarcinoma subtype, who had prior disease<br/>control on gefitinib. Presence of EGFR mutations predicted for disease<br/>control with gefitinib, and for disease control with erlotinib after<br/>gefitinib failure.</p><p>Conclusion: A significant proportion of<br/>typical gefitinib-sensitive Asian NSCLC patients can have disease<br/>control with erlotinib after gefitinib failure. The role of subsequent<br/>administration of a second EGFR TKI after failure of the first TKI in<br/>advanced NSCLC should be further pursued.</p><p>(C) 2008International Association for the Study of Lung Cancer</p><br/>亚洲非小细胞肺癌病人IRESSA耐药后，使用TARCEVA有效的证据 <br/> <br/>原文章<br/>杂志胸肿瘤。 3 （ 4 ） :400 - 404 ， 2008年4月。 <br/>黄，艾文 (台湾)<br/> <br/>摘要： <br/>导言：表皮生长因子受体（ EGFR ）酪氨酸激酶抑制剂（ tkis ）IRESSA(吉非替尼)和TARCEVA(埃罗替尼)正在取得越来越大的作用，在中晚期非小细胞肺癌（<br/>NSCLC ） 治疗中，有越来越多的兴趣集中在第一tki 失败后，使用第二个tki，尤其是在亚洲的病人中，预计会更有效。 <br/> <br/>方法：我们做了回顾性分析，研究了在过去2年中，在我们的机构中接受过吉非替尼治疗，也接受过埃罗替尼治疗的病人。在 病人做了肿瘤样本表皮生长因子受体基因突变分析后确认了对第一个tki药物耐药，病人收接受第二个 tki 。<br/> <br/>结果：<br/>分析中包括在了14例患者，所有这些人在吉非替尼进展后，都收到了埃罗替尼。其中中国血统，女性，从不吸烟者，腺癌    为主。吉非替尼疾病控制率为64.3 ％ （ 14 中9人） ， IRESSA 进展后， 使用TARCEVA的疾病控制率为35.7 ％ （  14 人中5人）。所有    IRESS耐药后TARCEVA有效的患者都是从未吸烟者并且是腺癌型，事先使用 IRESSA时都得到疾病控制。 并且使用IRESSA前，进行EGFR突变预测疾病控制时，以及 IRESSA耐药后，使用 TARCEVA前，进行EGFR突变预测疾病控制时，都存在 变异。 <br/><br/> 结论：大量的  对IRESSA敏感的亚洲非小细胞肺癌患者，在IRESSA耐药后，使用TARCEVA可以有疾病控制。在晚期非小细胞肺癌治疗中，在第一tki耐药后的第二个表皮生长因子受体tki，应进一步研究。 <br/> <br/> 2008international研究协会肺癌<p><br/></p><p><br/></p>
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URPOSE:<br/>Failure to gefitinib is generally believed to be associated with<br/>cross-resistance to other epidermal growth factor receptor tyrosine<br/>kinase inhibitors (EGFR-TKI). Here we report a case whose active<br/>EGFR-mutant NSCLC responded to erlotinib treatment. PATIENT AND<br/>METHODS: Lung specimen was obtained during diagnostic procedures from a<br/>41-year-old Taiwanese male smoker with adenocarcinoma. He received<br/>cisplatin-based chemotherapy following craniotomy to remove his brain<br/>metastasis. Tumor progressed in both lung and left adrenal gland. He<br/>underwent second-line docetaxel chemotherapy. Tumor progressed again 7<br/>months later. He was subsequently treated with gefitinib 250mg QD.<br/>Complete regression of the lung tumor and partial response of the left<br/>adrenal gland mass was achieved. Nine months later, the left lower lobe<br/>lung tumor and left adrenal gland tumor progressed. A lung biopsy from<br/>the left lower lobe disclosed an adenocarcinoma which harbored an<br/>in-frame deletion in exon 19 (heterozygous delE746-A750) of EGFR<br/>without a second mutation such as T790M in exon 20. Subsequent<br/>erlotinib 150mg QD was administered. He experienced grade 1 skin rash,<br/>diarrhea and paronychia following erlotinib. RESULTS: This patient<br/>achieved a partial response to erlotinib treatment. He remained on<br/>erlotinib for a total of 18 months until the left adrenal gland tumor<br/>progressed. CONCLUSIONS: This case demonstrated that NSCLC bearing<br/>in-frame deletion in exon 19 of EGFR may respond to erlotinib treatment<br/>following gefitinib failure.</p>非小细胞肺癌IRESSA耐药后TARCEVA效果，。 <br/>肺癌。 2007年12月; 58 （ 3 ） :414 - 7 。 epub 2007年7月6日。<br/><br/> <br/>常JW ，周  CL 等 <br/> 长庚医院，血液-肿瘤科，桃园，台湾。  wen1902@hotmail.com <br/><br/> <br/>目的：<br/>吉非替尼耐药被普遍认为是与之关联的其他表皮生长因子受体酪氨酸激酶抑制剂（表皮生长因子受体- tki ） 交叉 耐 药。  在这里我们报告一例，其非小细胞肺癌中积极的表皮生长因子受体突变体对埃罗替尼治疗作出回应。<br/>病人和方法：<br/>一个41岁的台湾男性吸烟与腺癌肺标本在诊断程序中被获得了。从他收到了顺铂为基础的化疗，又接受了开颅手术，以消除他的脑转移瘤。以后 肿瘤进展，在两个肺及左肾上腺。他经历了第二线多西紫杉醇化疗。经过七个月后肿瘤再次进展。其后他接受吉非替尼250mg每日1次治疗。完成肺肿瘤减小和左肾上腺肿块实现局部反应。九个月后，左下叶肺肿瘤和左肾上腺肿瘤的进展。从左下叶肺穿刺活检显示，腺癌被，包藏在一帧删除外显子19 （杂合子dele746 - a750 ）表皮生长因子受体，没有第二个突变，如t790m外显子20。随后采用埃罗替尼150mg每日1次。他 经历了一级皮疹，腹泻和甲沟炎。<br/>结果：<br/>这名病人，对埃罗替尼治疗取得了部分回应。他一直对埃罗替尼有反应，一共有18个月，直到左肾上腺肿瘤的进展。<br/>结论：<br/>这个病例表明，IRESSA耐药后，在非小细胞肺癌患者中，表皮生长因子受体的外显子19携带‘在帧删除’(IN-FRAME DELETION)的患者，可能对TARCEVA作出回应。<br/><br/><br/>