吸烟对吉非替尼联合放疗治疗化疗失败的Ⅲ、Ⅳ期非小细胞肺癌患者临床疗效的影响

Impact of smoking on the clinical efficacy of gefitinib combined with radiotherapy after chemotherapy failure in the patients with stages Ⅲ and Ⅳ non-small-cell lung cancer

目的应用吉非替尼联合放疗治疗既往含铂类化疗方案失败的Ⅲ、Ⅳ期非小细胞肺癌（NSCLC）患者,观察吸烟与不吸烟患者疗效、生存以及EGFR突变率的差异。方法 40例晚期NSCLC患者,吉非替尼250 mg/d,自放疗第1天开始口服直至放疗结束后60 d,联合胸腔放疗（4个剂量组）。收集患者组织27例,血浆40份,应用ARMS方法进行EGFR突变检测。结果不吸烟患者中,有效率35%,疾病控制率90%。吸烟患者中,有效率25%,疾病控制率75%。不吸烟与吸烟患者中位生存时间分别为14.6个月（95%CI：9.2~20.0个月）和10.7个月（95%CI：9.4~12.0个月）（P=0.8）;中位无疾病进展时间分别为6.9个月（95%CI：4.0~9.7个月）和4.5个月（95%CI：3.4~5.6个月）（P=0.7）,1年生存率两者分别为70%和45%。在27例可分析的组织标本以及40份血浆中,共检测出9例EGFR突变,包括6例19号外显子的缺失突变（Del 19突变）,2例21号外显子的L868R点突变以及1例T790M点突变。其中,与治疗有效相关的8例突变中,5例（25%,5/20）为不吸烟患者,3例（15%,3/20）为吸烟患者。结论在以吉非替尼为组成部分的综合治疗中,非吸烟患者治疗效果优于吸烟患者,EGFR突变发生率在非吸烟组明显高于吸烟组。

Objective To observe the clinical outcome and epidermal growth factor receptor（EGFR） mutation rate in smoking/never smoking advanced non-small-cell lung cancer（NSCLC） patients,who were treated with gefitinib and concurrent thoracic radiation（RT）.Methods Patients of this study had gefitnib oral tablet,250 mg/d,from the 1st day of RT until the 60th day after RT.Thoracic radiation was performed in four dose cohort.DNA was extracted from 27 tissue samples and 40 plasmas of 40 enrolled patients.Amplification Refractory Mutation System（ARMS） was used for analysis.Results In never smokers and smokers,response rate（RR）,disease control rate（DCR） were 5%,90% and 25%,75% respectively.Overall survival rate was 14.6 m（95% CI： 9.2-20.0 m）and 10.7 m（95% CI： 9.4-12.0 m）（P=0.8） respectively.One-year survival rate was 70% and 45% respectively.EGFR mutation was found in 9 patients.Six were exon 19 in-frame deletion.Two（5%） were exon 21 point mutation L858R.Meanwhile,and one less common point mutation T790M in exon 20 was also identified,which has been reported as one possible explanation for resistance to gefitinib.Five EGFR activating mutation occurred in never-smokers and 3 in smokers.Conclusion Never smoking NSCLC patients could get more benefits in gefitnib-based therapy than smoking patients.EGFR mutations are more frequent in never smokers.