Prospective validation for prediction of gefitinib sensitivity by epidermal growth factor receptor gene mutation in patients with non-small cell lung cancer
Prospective validation for prediction of gefitinib sensitivity by epidermal growth factor receptor gene mutation in patients with non-small cell lung cancer
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DOI：
10.1097/01243894-200701000-00006
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发表时间：
2007-01-01
影响因子：
20.4
通讯作者：
Hida, Toyoaki
中科院分区：
文献类型：
--
作者：
Yoshida, Kimihide;Yatabe, Yasushi;Hida, Toyoaki
我们前瞻性地评估了吉非替尼单药治疗晚期或预处理的表皮生长因子受体（EGFR）突变的非小细胞肺癌（NSCLC）患者的疗效。方法：采用片段分析法检测非小细胞肺癌患者EGFR外显子19缺失突变，采用环切酶聚合酶链反应技术检测EGFR L858R点突变。EGFR突变阳性的局部晚期、转移性或复发/难治性非小细胞肺癌患者无法通过手术或胸部放疗治愈，可接受250 mg/天的吉非替尼治疗，直至疾病进展。结果：66例患者中有27例（41%）检测到EGFR基因突变。10例外显子19缺失，17例L858R缺失。21名携带EGFR突变的患者接受吉非替尼治疗，其反应和不良事件被认为是可评估的。19例EGFR突变患者获得客观缓解（3例完全缓解，16例部分缓解），总缓解率为90.5%（95%可信区间69.6%-98.8%）。中位无进展生存期为7.7个月（95%置信区间，6.0个月至未达到）。中位总生存期尚未达到。常见的不良反应是皮肤毒性、腹泻和转氨酶升高，但未观察到肺毒性。结论：检测常见的EGFR突变似乎有助于选择可能受益于吉非替尼单药治疗的非小细胞肺癌患者。
Introduction: We evaluated the efficacy of gefitinib monotherapy prospectively in patients with advanced or pretreated non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations.Methods: Patients with NSCLC were examined for EGFR exon 19 deletion mutations by fragment analysis and for EGFR L858R point mutations by the Cycleave polymerase chain reaction technique. EGFR mutation-positive patients with locally advanced, metastatic, or recurrent/refractory NSCLC that was not curable with surgery or thoracic radiotherapy were candidates for gefitinib treatment administered at 250 mg/day until disease progression.Results: Mutations of the EGFR gene were detected in 27 (41%) of 66 patients. Ten had exon 19 deletion, and 17 had L858R. Twenty-one patients harboring EGFR mutations were treated with gefitinib and were considered assessable for responses and adverse events. Nineteen patients with EGFR mutations achieved objective responses (three complete responses and 16 partial responses), resulting in an overall response rate of 90.5% (95% confidence interval, 69.6%-98.8%). The median progression-free survival was 7.7 months (95% confidence interval, 6.0 mo to not reached). The median overall survival has not been reached. Common adverse events were skin toxicity, diarrhea, and elevated aminotransferases, but no pulmonary toxicity was observed.Conclusions: Detection of common EGFR mutations seems to be useful for selecting patients with NSCLC who would likely benefit from gefitinib monotherapy.