Germline polymorphisms in EGFR and survival in patients with lung cancer receiving gefitinib
Germline polymorphisms in EGFR and survival in patients with lung cancer receiving gefitinib
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DOI：
10.1038/sj.clpt.6100320
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发表时间：
2008-03-01
影响因子：
6.7
通讯作者：
Baker, S. D.
中科院分区：
文献类型：
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作者：
Gregorc, V.;Hidalgo, M.;Baker, S. D.
本研究的目的是评估在接受EGFR酪氨酸激酶抑制剂吉非替尼治疗的白色非小细胞肺癌（NSCLC）患者中，参与转录调控的生殖系表皮生长因子受体（EGFR）变异体与总生存率之间的相关性。在连续175例口服吉非替尼（250 mg/天）治疗的患者中，170例（中位年龄：67岁; 72%为男性）可评价基因分型和生存率。55例患者（33%）病情稳定，17例（10%）客观缓解。四种单倍型中最常见的是EGFR-216 G>T和-191 C>A位点的G-C（EGFR*1）（频率为0.45）。在调整体力状态为0或1的患者（N=139）的体力状态、既往含铂化疗以及第一个治疗周期内皮疹或腹泻的发生率后，EGFR*1的缺失与明显更好的生存率相关（风险比：0.54; 95%置信区间：0.32-0.91; P=0.015）。这些结果可能有助于确定可以从吉非替尼治疗中获益的NSCLC患者。
The purpose of this study was to evaluate associations between germline epidermal growth factor receptor (EGFR) variants involved in transcriptional regulation and overall survival in white patients with non-small-cell lung cancer (NSCLC) treated with the EGFR tyrosine kinase inhibitor, gefitinib. Of 175 consecutive patients treated with oral gefitinib (250mg/day), 170 ( median age: 67 years; 72% men) were evaluable for genotyping and survival. Fifty-five patients (33%) had stable disease and 17 (10%) had an objective response. The most common of four haplotypes was G-C (EGFR*1) at the EGFR -216G>T and -191C>A loci (frequency, 0.45). After adjusting for performance status, previous platinum-containing chemotherapy and occurrence of skin rash or diarrhea during the first treatment cycle in patients with performance status 0 or 1 (N=139), the absence of EGFR*1 was associated with significantly better survival ( hazard ratio: 0.54; 95% confidence interval: 0.32-0.91; P=0.015). The results may help identify patients with NSCLC who can benefit from gefitinib treatment.