Abraxane在胃癌及卵巢癌中的应用课件

1、Abraxane在胃癌及卵巢癌中的应用江苏省人民医院 束永前第1页，共31页。 紫杉类药物胃癌治疗评价第2页，共31页。目前常用化疗方案 ( 转移性/局部晚期胃癌 )一线5-FU/CAPE+DDP/EPI/OXA/DOC二线DOC/PACIRI国内胃癌化疗方案现状第3页，共31页。晚期胃癌一线治疗III期临床研究StudyRegimenNRR (%)p-valueMSTp-valueV3252006DCFCF2212243725.0129.2m 8.6m 0.02Kang Y2006XPFP16015641290.0310.5m 9.3 m0.27S. Al-Batran2006FLOFP98

2、10234270.0125.7(TTP)3.80.081Wasaburo2008S-1+PDDS-11451505431.00213.0m11.0 m0.04Cunningham 2008 ECFECXEOFEOX249241235239 40.746.442.447.9NS9.9 m9.9 m9.3m11.2 mNS 第4页，共31页。紫杉醇联合卡培他滨序贯卡培他滨维持方案一线治疗晚期胃癌的开放、非对照、多中心临床研究第5页，共31页。试验设计紫杉醇卡培他滨卡培他滨晚期/复发胃或胃食管结合部腺癌未接受过化疗，或经新辅助、辅助化疗结束超过6个月出现进展有可测量病灶KPS70重要脏器功能符合要求

3、4-6周期无进展直到进展或不能耐受毒性或撤出知情同意Cape1000mg/m2 bid d1-14PTX 80mg/m2 d1,8, Q3wCape1000mg/m2 bid d1-14第6页，共31页。研究初步结果181例，现可评价126例(其余正在随访中) CR 3例，PR 54例 (RR45.3%) SD 43例（36.8%） PD 25例（21.4）不良反应（3/4度，5%） 白细胞减少、中性粒细胞减少、脱发 III 期临床试验DCR 80.9%第7页，共31页。ML22697-III期多中心、随机、对照研究随机1:1紫杉醇卡培他滨 顺铂卡培他滨4周期直到进展或6周期后结束治疗卡培他滨

4、直到进展A组B组晚期/复发胃或胃食管结合部腺癌 未接受过化疗，或经新辅助、辅助化疗结束超过6个月出现进展N=320Start Date:November 2009 第8页，共31页。Abraxane治疗晚期胃癌应用经验（日本） Phase II Study of ABI-007 for Gastric Cancer Narikazu Boku, MDDivision of Gastrointestinal OncologyShizuoka Cancer Center, Japan第9页，共31页。Purpose The purpose of this study is to evaluate

5、the efficacy and safety of tri-weekly ABI-007 for recurrence or unresectable gastric cancer patients who have received one prior regimen containing fluoropyrimidine and developed disease progression or recurrence. 第10页，共31页。EndpointsPrimary endpoint:Overall response rateSecondary endpoints:SafetyPro

6、gression-free survival Overall survivalDisease control rateSample size: 53expected response rate 25%threshold 10%第11页，共31页。Eligibility Inclusion Criteria:Histologically or cytologically confirmed gastric adenocarcinoma Received one prior regimen containing fluoropyrimidine analogs and developed dise

7、ase progression or recurrence Age: 20 - 74 At least one measurable lesion by RECIST criteria 第12页，共31页。Eligibility Exclusion Criteria:History of Taxane use Patients with another active malignancy Pre-existing peripheral neuropathy of Grade 2 (CTCAE) Chronic treatment with steroids 第13页，共31页。Patient

8、CharacteristicsGender: M / F27 / 9 Age, years: Median (range)62 (34 73) PS: 0 / 1 / 222 / 14 / 0Primary lesion: - / +23 / 13Target: 1st line failure23: Adjuvant failure13Prior regimen: S-117: S-1+CDDP11: Xeloda+CDDP+Avastin 3: S-1+L-OHP 2: Others3Prior chemotherapy period, days: Median (range)175 (2

9、7 592)n = 36第14页，共31页。Treatment courseTreatment courseReasons for Discontinuation No. of Pts (%) 1:34 (100) 2:29(85) 3:22(65) 4:16(47) 5:10(29) 6:6(18) 7:6(18) 8:3(9) 9:3(9)10:1(3)11:1(3) No. of PtsDisease progression26Toxicity- Creatinine increase1- DVT*1Pts refusal1ABI-007, 260mg/m2, q3w* DVT：深静脉血

10、栓第15页，共31页。Progression Free Survival第16页，共31页。Response rate PRSDPDRRDCRn=327101522 %53 %No. of PtsPRSDPD1st line failure194(21%)87Adjuvant failure133(23%)282008.3.18 monitoring第17页，共31页。AdverseEvents G1G2G3G4All(%) G3(%)Neuropathy: sensory1711409111Neuropathy: motor5100170Myalgia14720666Arthralgia13

11、930719Rash111020666Pruritus8200290Neutropenia210857137Others ( 3): WBC decrease, Lymphopenia, Hb decrease, ALP increase, Amylase increase2008.3.5 monitoringn=35第18页，共31页。2nd line chemotherapy trials TherapynRR(%)DCR(%)PFS/TTP *(M)MST(M)1Boku (1999)CPT-11+CDDP1527672Sato (2002)CPT-11+CDDP2520608.93Ha

12、maguchi (2004)CPT-11+MMC4529674.1104Yamada (2001)TXL (q3w)262710.55Yamaguchi (2002)TXL (q3w)19266Arai (2003)TXL (weekly)3523653.46.87Hironaka (2006)TXL (weekly)3824402.1 *58J.-L. Lee (2007)TXT (q3w)4916.3572.5 *8.39Y. Bang (2007)Sunitinib424.8402.8 *11.71: J Clin Oncol 17:319-323 (1999)2: ASCO 21 #6

13、00 (2002)3: ASCO 20044: Ann Oncol 12:1133-1137 (2001)5: Gastric cancer 5:90-95 (2002) 6: ASCO 20037: Gastric cancer 9:14-8 (2006)8: Cancer Chemother Pharmacol9: ASCO 2007第19页，共31页。Abraxane治疗卵巢癌 第20页，共31页。白蛋白结合型紫杉醇治疗铂类敏感的复发性卵巢癌、腹膜癌和输卵管癌的II期临床研究M. G. Teneriello, P. C. Tseng, M. Crozier, C. Encarnacion

14、, K. Hancock, M. J. Messing, K. A. Boehm, A. Williams, D. Ilegbodu, L. AsmarTeneriello M, et al. Presented at ASCO Annual Meeting 2007; Abstract 5525第21页，共31页。研究目的和标准主要目的:总有效率 次要目的:PFSOSQOL安全性和毒性Teneriello M, et al. Presented at ASCO Annual Meeting 2007; Abstract 5525第22页，共31页。主要入组标准组织学或细胞学诊断的卵巢上皮癌、

15、输卵管癌或腹膜癌 （任何期别，如果是I期，则要求2-3级）RECIST标准可测量的病灶，在无可测量病灶的情况下，CA-125升高70曾接受铂类为主方案的化疗铂类治疗敏感（铂类为主方案化疗后无治疗时间长于6个月)ECOG 评分 (PS) 0-2如果有周围神经病变，级别低于1级Teneriello M, et al. Presented at ASCO Annual Meeting 2007; Abstract 5525第23页，共31页。主要排除标准首次治疗的I期1级患者未接受过化疗接受过1个以上方案化疗，或所用过的方案不是铂类为主的方案非上皮性肿瘤无可测量病灶且 CA-125 70入组6个月内

16、接受了紫杉类药物的治疗或曾使用过白蛋白结合型紫杉醇Teneriello M, et al. Presented at ASCO Annual Meeting 2007; Abstract 5525第24页，共31页。治疗计划经治医生决定是否使用预防用药患者在每周期的第1天使用白蛋白结合型紫杉醇 260 mg/m2 白蛋白结合型紫杉醇，30分钟内静注，21天为1周期患者每3周接受治疗直到已证明为进展或不可耐受的毒性或治疗已达6周期对于只有CA125升高无可测量病灶的患者，在进行疗效评价之前，由经治医生决定治疗的周期数，最多治疗3周期治疗达CR的患者，由经治医生决定是否再打两个周期。因此，CR的患

17、者可能接受最多8个周期的化疗Teneriello M, et al. Presented at ASCO Annual Meeting 2007; Abstract 5525第25页，共31页。患者的特征入组患者数47年龄 (岁)范围65.442 84人数百分比种族白种人黑人西班牙人亚裔印度人41131187.22.16.42.12.1ECOG 评分0138980.819.2既往治疗化疗间歇期 12 months化疗间歇期 12 months手术4344491.58.593.6原发病卵巢上皮癌输卵管癌腹膜癌371978.72.119.2组织学级别GX (不能评价)G1 (分化良好)G2 (中度

18、分化)G3 (分化差)丢失/不清14923102.18.519.248.921.3Teneriello M, et al. Presented at ASCO Annual Meeting 2007; Abstract 5525第26页，共31页。结果符合条件的/治疗的患者总数44N (%)95% CI最好的疗效完全缓解部分缓解稳定SD 6个月SD 6个月进展临床受益不可评价14 (31.8%)14 (31.8%)14 (31.8%)682 (4.5%)34 (77.3%)3(18.1 45.6)(18.1 45.6)(18.1 45.6)(0 10.7)起效时间 (月)中位范围1.8(0.6 3.4)疗效持续时间（月 )中位范围95% CI6.5(2.7 13.2)(6.6 N/A)Teneriello M, et al. Presented at ASCO Annual Meeting 2007; Abstract 5525第27页，共31页。最好疗效符合条件/治疗的患者总数: 44RECIST测量*CA-125值 RECIST测量和 CA-125值完全缓解167部分