摘要
目的 探讨中国人群中EGFR的突变与吉非替尼治疗局部晚期或转移性非小细胞肺癌(NSCLC)的疗效和预后的关系。方法 2002年5月至2005年2月,符合人组条件的患者每日服用吉非替尼,每次250mg,直至疾病进展或出现不可耐受的毒副反应。收集患者吉非替尼治疗前的肿瘤组织,提取基因组DNA后,采用巢式PCR技术扩增EGFR基因的18—24外显子,并从正反两个方向进行DNA测序和分析。结果 有106例患者人组,肿瘤标本包括25例冰冻的新鲜组织和81例石蜡包埋组织。其中32例(30.2%)发生了突变,腺癌患者的突变率(35.9%)明显高于鳞癌患者(14.3%,P=0.033)。突变患者的治疗有效率(71.9%)明显高于无突变患者(13.5%,P〈0.01)。突变患者的中位肿瘤进展时间(15个月)明显长于无突变患者(3个月,P〈0.01)。突变患者的生存期(18.5个月)也明显长于无突变患者(6.0个月,P〈0.01)。结论 中国人群中EGFR基因突变可以较好地预测吉非替尼治疗晚期NSCLC的疗效和预后。
Objective To investigate the correlation between mutation in EGFR tyrosine kinase domain and tumor response as well as prognosis in advanced stage non-small cell lung cancer ( NSCLC ) treated with iressa. Methods From May 2002 to Feb. 2005, iressa was orally administered at a dose of 250 mg once daily for 106 advanced stage NSCLC patients until occurrence of disease progression or intolerable toxicity. Cancer tissue was obtained from these patients, and DNA was extracted for analysis of mutation in exon 18 to 24 of EGFR. Exon 18 to 24 of EGFR were amplified by nest PCR, sequenced and analyzed from both sense and antisence directions. Results Primary NSCLC tissue specimens consisted of 25 frozen tissue blocks and 81 paraffin-embedded tumor tissue blocks from 106 consecutive NSCLC patients. Mutation was found to be more frequent in the adenocarcinoma than in the squamous cell carcinoma (35.9% vs 14.3% ,P = 0. 033 ). Mutation was identified in 32 patients (30.2%). Response rate to iressa was 71.9% in the patients with EGFR mutation versus 13.5% in those without mutation (P 〈0. 01 ). Compared with the patients without EGFR mutation, those with mutation had longer overall survival ( median, 13.45 vs. 5.25 months ; P〈0.01) andmedian time to progression (median, 8.35 vs. 3.0 months; P〈0. 01). Conclusion EGFR mutation may be positively correlated with the response and survival in advanced stage Chinese NSCLC patient treated with iressa.
出处
《中华肿瘤杂志》
CAS
CSCD
北大核心
2007年第4期278-283,共6页
Chinese Journal of Oncology
基金
全军“十一五”科技攻关项目(06G140)
关键词
吉非替尼
表皮生长因子受体
基因突变
非小细胞肺癌
预后
Gefitinib
Epidermal growth factor receptor
Mutation
Non-small-cell lung cancers
Prognosis