1.2专题讲座2、肿瘤的个体化治疗.ppt

* * 中低ERCC1 mRNA表达的患者有更长的无疾病进展生存时间(p0.001)，高ERCC1 mRNA表达的患者复发的危险性是低表达者的3.06倍。然而，在76例顺铂加紫杉醇治疗的患者中，ERCC1 (Asn118Asn)和mRNA的表达与生存没有关系。这个结果提示我们紫杉醇可能干扰ERCC1的表达，临床上对顺铂加其它药物联合治疗耐受的患者可能对顺铂加紫杉醇联合治疗是有效的。在75例进行了铂类药联合紫杉醇的术后辅助化疗的患者中，未见? III–tubulin mRNA与治疗疗效和生存的相关性；然而在103例进行了铂类药联合其他非紫杉醇的术后辅助化疗的患者中，高表达? III–tubulin mRNA的患者疗效比低表达的患者差，p=0.030，而且疾病进展的风险是低表达患者的3.01倍，95% CI: 1.48-6.11, p=0.002，结果提示紫杉醇可能逆转? III–tubulin-相关的铂类药物耐受。 * * Median survival exceeded 28 months for 12 patients with EGFR mutations, and was 11 months for 38 patients with low BRCA1, 9 months for 40 patients with intermediate BRCA1, and 11 months for 33 patients with high BRCA1. Two-year survival was 73.3%, 41.2%, 15.6% and 0%, respectively. Median survival was influenced by RAP80 expression in the three BRCA1 groups. For example, for patients with both low BRCA1 and low RAP80, median survival exceeded 26 months. * 浙江省肿瘤医院 * * 浙江省肿瘤医院 * * * * * * * * 药物遗传学与个体化治疗 药物吸收、分布、代谢、分泌相关基因 代谢酶基因 药物作用靶点下游信号通路 细胞色素P450酶 谷胱甘肽S-转移酶（GST） 二氢嘧啶脱氧酶（DPD） 尿苷二磷酸-葡萄糖醛酸转移酶（UGT） 胸苷磷酸化酶（TP） * Explaining Interindividual Variability of Docetaxel Pharmacokinetics and Pharmacodynamics in Asians Through Phenotyping and Genotyping Strategies. Boon-Cher Goh, et al. J. Clin. Oncol., 2002; 20: 3683 - 3690. Randomized Pharmacokinetic and Pharmacodynamic Study of Docetaxel: Dosing Based on Body-Surface Area Compared With Individualized Dosing Based on Cytochrome P450 Activity Estimated Using a Urinary Metabolite of Exogenous Cortisol. Noboru Yamamoto, et al. J. Clin. Oncol., 2005; 23: 1061 - 1069. * 试验设计 * * A phase Ⅱ pharmacodynamics and pharmacokinetics study of gemcitabine plus cisplatin in patients with advanced non-small cell lung cancer?  Zhejiang Cancer Hospital * Gemcitabine 1250mg/m2 i.v.,d1,5 repeat every 3 weeks cisplatin 75mg/m2 i.v.,d1 * Results Patient?characteristics(N=28) Characteristics?????????????? ??Number??????????????? ?????Ratio% Age（year）??????????????????? ?Median?????????????????