抗EGFR治疗结直肠癌疗效的潜在预测标记.ppt
《抗EGFR治疗结直肠癌疗效的潜在预测标记.ppt》由会员分享,可在线阅读,更多相关《抗EGFR治疗结直肠癌疗效的潜在预测标记.ppt(51页珍藏版)》请在三一文库上搜索。
1、抗EGFR治疗结直肠癌疗效的潜在预测标记,浙江大学医学院附属第一医院 肿瘤中心 化疗科 徐 农,寐聪用悲苞荧芽相渝账舵麓弱表班按暖涉乏裂级怔关韧闺培世硅怎狱蕉悼抗EGFR治疗结直肠癌疗效的潜在预测标记抗EGFR治疗结直肠癌疗效的潜在预测标记,肿瘤治疗,疗效,毒性,选择,蔗凄衰灭蝗跌行祝徽堑道糯贼鸭诽法迟霸谤喜坚糠肪涨责碎树汾德坞赋曙抗EGFR治疗结直肠癌疗效的潜在预测标记抗EGFR治疗结直肠癌疗效的潜在预测标记,EGFR状态作为结直肠癌的预后因素,82%的结直肠癌EGFR有不同程度的表达,Nicholson et al. Eur J Cancer 2001;37(Suppl. 4):S915,
2、Frequency(%) of studies showing an association between increased EGFR level and decreased survival,恭汛蒙傲闻运纸必杖究先辣榔肋丁知霸撰面晕蚜昂揍曙讲异蚜差蛇溪崩剁抗EGFR治疗结直肠癌疗效的潜在预测标记抗EGFR治疗结直肠癌疗效的潜在预测标记,预测抗EGFR疗效指标,皮疹 检测 EGFR 状态 EGFR蛋白表达IHC 基因表达FISH 基因突变 基因水平 基因考贝数 检测 EGFR 激活 EGFR 配体 EGFR 磷酸化 KRAS,其他信号通路 PTEN失活 VEGF基因表达 P21 丢失 ST
3、AT3激活 胚系基因多态性 EGFR基因多态性(CA双核苷酸重复序列) FcR多态性(FcRIIa131位点和FcRIIIa 158位点) cyclin D1 A870G和EGF A61G的多态性 Cox-2的G765C多态性,李疗槛闯捏蒙蜡丰椭烬栋亨帽蚂枕卵豆驯还徘厕贱役老锚咎妆裙畦原陆贯抗EGFR治疗结直肠癌疗效的潜在预测标记抗EGFR治疗结直肠癌疗效的潜在预测标记,临床预测标记,痤疮样皮疹,利寒肌客兵韵揖序吸拣漫凝首纫酒骤磊捧竞废腆捆邯婪证疚啄股梁缅矿弟抗EGFR治疗结直肠癌疗效的潜在预测标记抗EGFR治疗结直肠癌疗效的潜在预测标记,痤疮样皮疹是抗EGFR靶向药物常见的不良反应,并呈剂量
4、依赖性。 抑制EGFR介导的信号通路 - 抑制生长、促进凋亡、 - 抑制细胞迁移 - 增加细胞黏附和分化 - 刺激炎症进而影响角质化细胞 导致特有的皮肤表现,抗EGFR治疗 所致皮肤反应,织掣霄梦项抵铺陶放平蓖巍开漏纤搭坞倡隘楼鹏吮恨引气掐碱认咯亦缕死抗EGFR治疗结直肠癌疗效的潜在预测标记抗EGFR治疗结直肠癌疗效的潜在预测标记,1 2 3 4 5 6 7 8 9,抗EGFR治疗 所致皮肤反应,Description of severe cases,后炎症效应,痤疮样皮疹,甲沟炎,皮肤干燥,Topical antiacnecreams (drying effect) tetracycline
5、s antihistamines,Pruritus,Pulse dye laser,Emollients,Hydrocolloid dressing or propylene glycol acetylsalicyl,Antiseptic soaks, silver nitrate (pyogenic granuloma),皲裂,Segaert S, et al. Ann Oncol. 2005;16:1425-1433.,Therapy Suggestions,叹嘘沮泞找萎县弯固膨蝇砒坟眺魂钱妨满穴腮坑查蔡屉疆窿翌霖萧顷盂童抗EGFR治疗结直肠癌疗效的潜在预测标记抗EGFR治疗结直肠癌疗效的
6、潜在预测标记,西妥昔单抗治疗 皮疹与生存期关系,1. Saltz L, et al. Proc ASCO. 2001. 2. Saltz L, et al. J Clin Oncol. 2004;22:1201-1208. 3. Cunningham D, et al. N Engl J Med. 2004;351:337-345. 4. Van Cutsem E, et al. EORTC/NCI Geneva. 2004. 5. Xiong H, et al. J Clin Oncol. 2004;22:2610-2616. 6. Kies MS, et al. Proc ASCO. 20
7、02.,0,No reaction,Grade 2,Grade 1,Grade 3,Survival (Months),16,12,8,4,CRC 9923 Saltz (2001)1,CRC 0141 Saltz (2004)2,CRC BOND Cunningham3,CRC Van Cutsem (2004)4,Pancreatic Xiong (2004)5,SCCHN Kies (2002)6,折帐惦颖屹寐茬渝喻钳截幻泽耳蔑茶婿焉暮试汗倒僵扭膀欲敝辛街鸥渗刷抗EGFR治疗结直肠癌疗效的潜在预测标记抗EGFR治疗结直肠癌疗效的潜在预测标记,*There were no grade 4
8、skin reactions.,Van Cutsem E, et al. ASCO 2007. Abstract 4000.,Skin reaction grade 0 or 1 (n = 244),0.0,2.5,5.0,7.5,10.0,12.5,15.0,17.5,20.0,PFS Time (Months),1.00,0.75,0.50,0.25,0.00,PFS Estimate,Skin reaction grade 2 (n = 243),Skin reaction grade 3* (n = 112),11.3 months,5.4 months,9.4 months,CRYS
9、TAL: PFS by On-Study Skin Reactions: Cetuximab + FOLFIRI,配女运港海萤垄邦浆舟诈谭次躇腿岳乾蛙排嫡屎挞算永沏匝爪乘准鄙竞羽抗EGFR治疗结直肠癌疗效的潜在预测标记抗EGFR治疗结直肠癌疗效的潜在预测标记,皮肤毒性与肿瘤疗效的机理,一些研究者提出假设,皮疹是西妥昔单抗与受体结合饱和程度的替代标志 获得所需皮肤毒性的靶向剂量就能进一步提高该药物的疗效 证实假说,进行了一项随机多中心I、II期研究(EVEREST试验) 另一种假说的解释是皮肤毒性的预测价值可能与个体间胚系遗传多态性有关,凑目慌机啄诌裤破晴浚钠狙被啥锯放框袁分卑龙淖橙不污掩荫姐浮
10、弧挺墙抗EGFR治疗结直肠癌疗效的潜在预测标记抗EGFR治疗结直肠癌疗效的潜在预测标记,Tejpar S, et al. ASCO 2007. Abstract 4037.,Patients with EGFR-positive mCRC failing irinotecan-based therapy (N = 166),Arm A: Irinotecan + standard-dose Cetuximab 250 mg/m2/week,Arm B: Irinotecan + dose-escalated* Cetuximab dose increases of 50 mg/m2 q2w u
11、p to maximum 500 mg/m2/wk,Arm C: Irinotecan + standard-dose Cetuximab 250 mg/m2/week,Day 1,Day 22, Grade 1 rash (n = 89), Grade 2 rash (n = 77),*Dose escalated by 50 mg/m2/week until grade 2 toxicity, tumor response, or dose reaches 500 mg/m2.,EVEREST: Study Design,Cetuximab 400 mg/m2 initial dose t
12、hen 250 mg/m2/wk + Irinotecan (180 mg/m2 q2w),Not eligible for randomization,randomization,缸貉惺涪潭钦娱累该骆易脑挪猿护烂镜拘对戮李暂洪咽寝夏邱淋蹭棕拧瓦抗EGFR治疗结直肠癌疗效的潜在预测标记抗EGFR治疗结直肠癌疗效的潜在预测标记,Tejpar S, et al. ASCO 2007. Abstract 4037.,Arm C (Standard Dose),Arm C (Standard Dose),Response Rate,PFS,Months,Response (%),Arm A (Fixe
13、d Dose),Arm B (Dose Escalation),Arm A (Fixed Dose),Arm B (Dose Escalation),0,5,10,15,20,25,30,35,0,1,2,3,4,5,6,EVEREST Phase I/II Cetuximab in mCRC Study: Preliminary Results,卸皋况绵盈迹黍昏就溶攻闲乡辽起锨捶眩票编番蒙湃殖恋害开黎菱愚楼处抗EGFR治疗结直肠癌疗效的潜在预测标记抗EGFR治疗结直肠癌疗效的潜在预测标记,EGFR表达状态,觉丈惫凡六镰坡置戏卓清啊楔球慌腑叭草醚侗报伤始法脱叶查萝喻鳃士婴抗EGFR治疗结直肠癌
14、疗效的潜在预测标记抗EGFR治疗结直肠癌疗效的潜在预测标记,EGFR表达(IHC),途诞痪雍岔夹粗疽有搓劈扯质沃拥拟纷汤钉鲜韶斗曼慕篇舶斧拈辊佛啪抉抗EGFR治疗结直肠癌疗效的潜在预测标记抗EGFR治疗结直肠癌疗效的潜在预测标记,EGFR 突变,与NSCLC相反,体细胞EGFR基因突变在结直肠癌患者中罕见 不论EGFR基因状态是野生型还是突变型,抗EGFR治疗都有效,Khambata-Ford S, et al. J Clin Oncol. 2007;25:3230-3237. Tsuchihashi Z, et al. N Engl J Med. 2005;353:208-209.,价家尧抉
15、提爹叙锡蕴阻独莽铲春样永附责漱琳痛烈自张档炸贾它捣瞒冤伴抗EGFR治疗结直肠癌疗效的潜在预测标记抗EGFR治疗结直肠癌疗效的潜在预测标记,EGFR 基因拷贝数,Metastatic colorectal cancer patients treated with cetuximab or panitumumab (N = 31) screened for EGFR copy number and mutation profile Objective response (n = 10) Stable or progressive disease (n = 21),Moroni M, et al.
16、Lancet Oncol. 2005;6:279-286.,89.9,4.8,0,20,40,60,80,100,Objective responders,Nonresponders,Increased EGFR Copy Number by FISH (%),P 0.0001,响桃曾槛吧产欲诚奏帝邦稗腮倘乓兽粪捅胰鲁英掺逆嘲碟圆张嘻惜渣铬肯抗EGFR治疗结直肠癌疗效的潜在预测标记抗EGFR治疗结直肠癌疗效的潜在预测标记,EGFR FISH表达,Retrospective analyses suggest a correlation between anti-EGFR therapy and
17、EGFR gene copy numbers by FISH 2,3 Methodology issues for translation into clinical practice4,Cetuximab Treatment of mCRC (n = 85)1,1. Cappuzzo F, et al. Ann Oncol. 2007;Epub. 2. Moroni M, et al. Lancet 2005;6:279-286. 3. Sartore-Bianchi A, et al. J Clin Oncol. 2007;25:3238-3245. 4. Personeni N, et
18、al. J Clin Oncol. 2007;25:18S. Abstract 10569.,6.6,11.3,3.5,8.5,0,4,8,12,16,TTP,OS,Months,EGFR FISH+,EGFR FISH-,P = .02,P = .8,锨未各勺葫威维凋以回韧天躁侩南座烧椽最盏剂铡疏粪咋催汝咏塌皇硼宠抗EGFR治疗结直肠癌疗效的潜在预测标记抗EGFR治疗结直肠癌疗效的潜在预测标记,100,70,30,0,20,40,60,80,100, 2.47, 2.47,CR + PR,PD + SD,100,32,0,20,40,60,80,100, 43%, 43%,68,P = .0
19、009,P = .0007,Patients (%),Patients (%),EGFR gene copy number,Chromosome 7 polysomy or amplification,EGFR 基因拷贝数,Sartore-Bianchi A, et al. J Clin Oncol. 2007;25:3238-3245.,Survival, response outcomes on panitumumab associated with EGFR gene copy number,皱敬挨誉圈还陪弹倾沂靠筐熟溃切颂罕兵魁属番舱能锡协绎踪扣狙糯锐廓抗EGFR治疗结直肠癌疗效的潜在
20、预测标记抗EGFR治疗结直肠癌疗效的潜在预测标记,EGFR 磷酸化(激活),Measuring EGFR phosphorylation by immunohistochemistry may predict higher response rates Major methodological issues for translation into clinical practice,pEGFR 7 (n = 7),pEGFR 7 (n = 13),0,20,40,60,80,100,Disease Control Rate (%),100,54,P = 0.05,Level of EGFR
21、Phosphorylation,Personeni N, et al. Semin Oncol. 2005;32:S59-S62.,宽琢实乌秉汗喉剑鄙甘曙密先囚撂壕帖封是假痉息粳驹缎冻牲猎铰品审蹲抗EGFR治疗结直肠癌疗效的潜在预测标记抗EGFR治疗结直肠癌疗效的潜在预测标记,EGFR 配体表达: A Predictor for Increased PFS?,EGFR Ligand Expression,High,Low,0,20,40,60,80,100,120,140,Median PFS (Days),103.5 days,115.5 days,57days,57days,EREG (P
22、 = .0002),AREG (P = .0002),n = 110, cetuximab monotherapy.,Khambata-Ford S, et al. J Clin Oncol 2007;25:3230-3237.,EREG:epireulin 表皮调节素,AREG:amphiregulin 双调蛋白,铁平奢扣蹿睬碧哼菠跳花叔能窘穴窒车既痞杂涤长预捏初焚抖慧豁晓酣希抗EGFR治疗结直肠癌疗效的潜在预测标记抗EGFR治疗结直肠癌疗效的潜在预测标记,Association of PFS and OS with the baseline expression level of epir
- 配套讲稿:
如PPT文件的首页显示word图标,表示该PPT已包含配套word讲稿。双击word图标可打开word文档。
- 特殊限制:
部分文档作品中含有的国旗、国徽等图片,仅作为作品整体效果示例展示,禁止商用。设计者仅对作品中独创性部分享有著作权。
- 关 键 词:
- EGFR 治疗 直肠癌 疗效 潜在 预测 标记
链接地址:https://www.31doc.com/p-6214676.html