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Analysis of EGFR inhibitor and/or COX-2 inhibitor sensitivity for clinical application in lung cancer.

EGFR抑制剂和/或COX-2抑制剂在肺癌临床应用的敏感性分析。

基本信息

批准号：
17590811
负责人：
HIDA Toyoaki
金额：
$ 2.18万
依托单位：
Aichi Cancer Center Research Institute
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2006
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17590811/
关键词：
Lung cancer Molecular targeted therapy COX2 inhibitor EGFR inhibitor Growth suppression Combination Gene mutation Clinical trial COX-2阻害剤 EGFR阻害剤抗癌剤

项目摘要

We performed mutational analyses of exon 19 deletion and the L858R point mutation of the EGFR gene. Exon 19 deletion was determined by common fragment analysis, and L858R mutation was detected by the cycleave real-time quantitative PCR technique. Using this method, 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. 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 (CI), 69.6%-98.8%). The median progression-free survival was 7.7 months (95% CI, 6.0 months to not reached). We also studied 14 tumors with acquired resistance to gefitinib for secondary mutations occurring in the EGFR tyrosine kinase domain. Seven of the 14 tumors had a secondary T790M mutation. Because our present study also indicated the cooperative inhibitory effect by simultaneously blocking EGFR-and COX-2-mediated pathways, combination of EGFR inhibitor and COX-2 inhibitor may provide a promising strategy for lung cancer therapy.

我们对EGFR基因的19号外显子缺失和L 858 R点突变进行了突变分析。通过共同片段分析确定第19号外显子缺失，通过cycleave实时定量PCR技术检测L 858 R突变。使用这种方法，我们前瞻性地评估吉非替尼单药治疗携带表皮生长因子受体（EGFR）突变的晚期或预治疗非小细胞肺癌（NSCLC）患者的疗效。66例患者中有27例（41%）检测到EGFR基因突变。10例有外显子19缺失，17例有L 858 R。21例携带EGFR突变的患者接受吉非替尼治疗，并被认为是可评估的反应和不良事件。19例EGFR突变患者达到客观缓解（3例完全缓解和16例部分缓解），总缓解率为90.5%（95%置信区间（CI），69.6%-98.8%）。中位无进展生存期为7.7个月（95% CI，6.0个月至未达到）。我们还研究了14例对吉非替尼产生获得性耐药的肿瘤中EGFR酪氨酸激酶结构域发生的继发性突变。14例肿瘤中有7例有继发性T790 M突变。同时阻断EGFR和考克斯-2通路，具有协同抑制作用，联合应用EGFR抑制剂和考克斯-2抑制剂有望成为肺癌治疗的新策略。