DNA直接测序技术检测EGFR基因突变指导厄洛替尼一线治疗晚期非小细胞肺癌的临床观察

目的：通过对晚期非小细胞肺癌（non-small cell lung cancer,NSCLC）患者表皮生长因子受体（epi-dermal growth factor receptor,EGFR）基因突变的检测,探讨厄洛替尼（Erlotinib）一线治疗晚期NSCLC的疗效与安全性。方法：从110例NSCLC患者的肿瘤组织提取DNA,用DNA直接测序技术检测EGFR基因19、21外显子突变情况,31例EGFR基因突变患者中,30例患者口服厄洛替尼150mg/d,持续至疾病进展或发生不能耐受的药物不良反应,评价客观有效率（RR）,疾病控制率（DCR）,总生存（OS）,无疾病进展时间（PFS）,一年生存率和药物不良反应。结果：110例NSCLC组织中EGFR基因突变31（28%）例,其中19外显子缺失18（58%）例,21外显子点突变13（42%）例。EGFR基因突变率女性40%、肺腺癌33%、不吸烟者46%,高于男性、非腺癌、吸烟的病人。30例口服厄洛替尼患者,完全缓解（CR）3例,部分缓解（PR）21例,疾病稳定（SD）5例和疾病进展（PD）1例,客观有效率为80%,疾病控制率为97%,截止随访结束,仍有20例患者生存,故中位总生存未获得结果,无疾病进展时间为11.4个月,1年生存率为78%,厄洛替尼治疗晚期NSCLC最常见的不良反应是腹泻和皮疹,多为I-II级。结论：DNA直接测序检测晚期NSCLC患者EGFR基因突变具有高度敏感性,以EGFR基因突变结果为依据,一线应用厄洛替尼治疗晚期NSCLC患者,疗效明显,耐受性好,是治疗晚期NSCLC的最佳选择之一。

Clinical observance of Erlotinib as first-line therapy for advanced non-small cell lung cancer directed by epidermal growth factor receptor mutations examined by direct sequence of DNA

Objective：To study mutations in exons 19,21 of epidermal growth factor receptor（EGFR） gene in advanced non-small cell lung cancer（NSCLC）,and evaluate the efficacy and safety of erlotinib as first-line therapy for advanced NSCLC.Methods：From November 2007 to January 2009,a total of 110 advanced NSCLC patients were selected DNA was extracted from paraffin-embedded tissues and exons 19,21 of the EGFR mutations were analysed by direct sequence of PCR products.There were 31 patients with EGFR mutation,30 of them were treated with 150 mg oral doses of erlotinib once daily until the disease progression or intolerable toxicity.To observe response rate（RR）,disease controle rate（DCR）,overall suvival（OS）,free progression-free survival（PFS）,1-year survival（1Y-S） and toxicity.Results：There were 31 EGFR mutations（28%） in 110 patients,including 18（58%） cases of inframe deletion del E746-A750 in exon19 mainly and 13（42%） cases of substitution in exon 21（all are L858R）with EGFR mutation.EGFR mutation was higher in females 40%（21/53）,adenocarcinoma 33%（30/92）and no-smokers 46%（22/48）than that in males,non-adenocarcinoma and smokers.A total of 30 advanced NSCLC patients with EGFR mutations were enrolled and treated with erlotinib.In these 30 patients,3 cases had complete response,21 had partial response and 5 had stable disease,1 had progressive disease.The response rate（RR） and disease control rate（DCR） after administration of erlotinib were 80%（24/30） and 97%（29/30）,respectively.To date,twenty patients are still alive.Hence,the median OS has not yet been reached,the media progression-free survival time（PFS） were11.4（95%CI：10.9-11.9） months.The one-year survival rate was 78%（95%CI：63.2-93.5）.The most common side effects were rash（60%） and diarrhea（20%）,however,most of the toxicities usually were mild.Conclusion： It was highly effective to use direct sequence of DNA from advanced NSCLC specimens to determine EGFR mutations.This study showed that erlotinib is very effective and well tolerated as first-line therapy for advanced NSCLC based on their EGFR mutation status.Erlotinib is one of the best drug for the treatment of advanced NSCLC patients.