课件：晚期非小细胞肺癌内科治疗的个体化.pptVIP

This slide introduces us to the pivotal BR.21 study, a prospective, randomized, phase 3 trial of erlotinib vs placebo. Patients were randomised (2:1 ratio) to treatment with either oral TarcevaTM 150mg daily or placebo. Stratification was on the basis of study centre, performance status, response to prior treatment, number of prior regimens and prior platinum therapy. 晚期非小细胞肺癌内科治疗的个体化 同济大学附属上海市肺科医院 周彩存 晚期非小细胞肺癌的治疗现状 Platinum-based doublets improve overall survival Prolonged chemotherapy more than 3-4 cycles could not further improve efficacy Doublets plus avastin or cetuximab improve overall survival compared with doublets Chemotherapy could improve disease-related symptoms Chemotherapy has toxicities Advanced lung cancer could not be cured and our aim is to make it chronic disease 个体化治疗 Definition - 4R: Right agent, right dose, right patients and right timing - Biomarkers：predictive, prognostic - Purpose: improvement of efficacy of therapy Advantages？ -Informative treatment strategy -Better treatment outcome -Less risk of toxicities -Decrease in cost 我院开展的晚期NSCLC药物基因组学个体化研究 ERCC1 RRM1 BRCA1 SNP of DNA repair genes ERCC1和XRCC3基因多态性在晚期接受含铂方案化疗病人中的疗效预测作用 Published in JJCO 研究方案及流程 2005.9月 to 2007.6月 IIIB/IV期 NSCLC Chemo-na?ve 重要脏器功能正常 无脑转移， 脊髓压迫 检测外周血白细胞 ERCC1 118和 XRCC3 241 单核 苷酸多态性 NP (N=53) GP(N=46) TP(N=31) DCR 85.4% PR 20% SD 65.4% PD 14.6% 1线化疗方案 N=130 Taqman 探针 Taqman探针结合实时荧光PCR方法与直接测序法一致 Figure 1 Real-time PCR reaction curves and sequencing profile of ERCC1 codon 118 (A )homozygous wide genotype.(B)heterozygous genotype.(C) homozygous variant genotype Figure 2 Real-time PCR reaction curves and sequencing profile of XRCC3 coden 241(A) homozygous wide genotype.(B) heterozygous genotype.(C)homozygous variant genotype ERCC1 118 XRCC3 241 基线特征及SNP分布 Genotyping Male Female Age Adeno Squam