胃癌及卵巢癌中的應(yīng)用ppt課件

1、Abraxane在胃癌及在胃癌及卵巢癌中的運(yùn)用卵巢癌中的運(yùn)用江蘇省人民醫(yī)院江蘇省人民醫(yī)院 束永前束永前 紫杉類藥物胃癌治療評(píng)價(jià)紫杉類藥物胃癌治療評(píng)價(jià)目前常用化療方案目前常用化療方案 ( 轉(zhuǎn)移性轉(zhuǎn)移性/部分晚期胃癌部分晚期胃癌 )一線一線5-FU/CAPE+DDP/EPI/OXA/DOC二線二線DOC/PACIRI國內(nèi)胃癌化療方案現(xiàn)狀國內(nèi)胃癌化療方案現(xiàn)狀晚期胃癌一線治療晚期胃癌一線治療III期臨床研討期臨床研討紫杉醇結(jié)合卡培他濱序貫卡培他濱紫杉醇結(jié)合卡培他濱序貫卡培他濱維持方案一線治療晚期胃癌的維持方案一線治療晚期胃癌的開放、非對(duì)照、多中心臨床研討開放、非對(duì)照、多中心臨床研討實(shí)驗(yàn)設(shè)計(jì)實(shí)驗(yàn)設(shè)計(jì)紫杉

2、醇卡培他濱紫杉醇卡培他濱卡培他濱卡培他濱晚期晚期/ /復(fù)發(fā)胃或胃食管結(jié)合部腺復(fù)發(fā)胃或胃食管結(jié)合部腺癌癌未接受過化療，或經(jīng)新輔助、未接受過化療，或經(jīng)新輔助、輔助化療終了超越輔助化療終了超越6 6個(gè)月出現(xiàn)進(jìn)個(gè)月出現(xiàn)進(jìn)展展有可丈量病灶有可丈量病灶KPS70KPS70重要臟器功能符合要求重要臟器功能符合要求4-6周期無進(jìn)展周期無進(jìn)展直到進(jìn)展或不能耐受毒性或撤出知情贊同直到進(jìn)展或不能耐受毒性或撤出知情贊同Cape1000mg/m2 bid d1-14PTX 80mg/m2 d1,8, Q3wCape1000mg/m2 bid d1-14研討初步結(jié)果研討初步結(jié)果181例，現(xiàn)可評(píng)價(jià)例，現(xiàn)可評(píng)價(jià)126例例(其

3、他正在隨訪中其他正在隨訪中) CR 3例，例，PR 54例例 (RR45.3%) SD 43例例36.8% PD 25例例21.4不良反響不良反響3/4度，度，5% 白細(xì)胞減少、中性粒細(xì)胞減少、脫發(fā)白細(xì)胞減少、中性粒細(xì)胞減少、脫發(fā) III 期臨床實(shí)驗(yàn)期臨床實(shí)驗(yàn)DCR 80.9%ML22697-III期多中心、隨機(jī)、對(duì)照研討期多中心、隨機(jī)、對(duì)照研討隨隨機(jī)機(jī)1:1紫杉醇卡培他濱紫杉醇卡培他濱 順鉑卡培他濱順鉑卡培他濱4周期周期直到進(jìn)展直到進(jìn)展或或6周期后周期后終了治療終了治療卡培他濱卡培他濱直到進(jìn)展直到進(jìn)展A組組B組組 晚期晚期/復(fù)發(fā)胃或胃食管結(jié)合部腺癌復(fù)發(fā)胃或胃食管結(jié)合部腺癌 未接受過化療，或經(jīng)

4、新輔助、輔助化療終了超越未接受過化療，或經(jīng)新輔助、輔助化療終了超越6個(gè)月出現(xiàn)進(jìn)展個(gè)月出現(xiàn)進(jìn)展N=320Start Date: November 2021 Abraxane治療晚期胃癌運(yùn)用閱歷日本治療晚期胃癌運(yùn)用閱歷日本 Phase II Study of ABI-007 for Gastric Cancer Narikazu Boku, MDDivision of Gastrointestinal OncologyShizuoka Cancer Center, JapanPurpose The purpose of this study is to evaluate the efficacy

5、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. EndpointsPrimary endpoint:Overall response rateSecondary endpoints:SafetyProgression-free survival

6、Overall survivalDisease control rateSample size: 53expected response rate 25%threshold 10%Eligibility Inclusion Criteria:Histologically or cytologically confirmed gastric adenocarcinoma Received one prior regimen containing fluoropyrimidine analogs and developed disease progression or recurrence Age

7、: 20 - 74 At least one measurable lesion by RECIST criteria Eligibility Exclusion Criteria:History of Taxane use Patients with another active malignancy Pre-existing peripheral neuropathy of Grade 2 (CTCAE) Chronic treatment with steroids Patient CharacteristicsGender: M / F27 / 9 Age, years: Median

8、 (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 (27 592)n = 36Treatment courseTreatment courseReasons f

9、or 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：深靜脈血栓Progression Free SurvivalResponse rate PRSDPDRRDCRn=327101522

10、%53 %No. of PtsPRSDPD1st line failure194(21%)87Adjuvant failure133(23%)282021.3.18 monitoringAdverse Events G1G2G3G4All(%) G3(%)Neuropathy: sensory1711409111Neuropathy: motor5100170Myalgia14720666Arthralgia13930719Rash111020666Pruritus8200290Neutropenia210857137Others ( 3): WBC decrease, Lymphopenia

11、, Hb decrease, ALP increase, Amylase increase2021.3.5 monitoringn=352nd line chemotherapy trials TherapynRR(%)DCR(%)PFS/TTP *(M)MST(M)1Boku (1999)CPT-11+CDDP1527672Sato (2002)CPT-11+CDDP2520608.93Hamaguchi (2004)CPT-11+MMC4529674.1104Yamada (2001)TXL (q3w)262710.55Yamaguchi (2002)TXL (q3w)19266Arai

12、(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 #600 (2002)3: ASCO 20044: Ann Oncol 12:1133-1 (2001)5: Gastric cancer 5:90-95 (2002) 6: ASCO 20037: Gast

13、ric cancer 9:14-8 (2006)8: Cancer Chemother Pharmacol9: ASCO 2007Abraxane治療卵巢癌治療卵巢癌 白蛋白結(jié)合型紫杉醇治療鉑類敏感的復(fù)發(fā)性卵巢癌、白蛋白結(jié)合型紫杉醇治療鉑類敏感的復(fù)發(fā)性卵巢癌、腹膜癌和輸卵管癌的腹膜癌和輸卵管癌的II期臨床研討期臨床研討M. G. Teneriello, P. C. Tseng, M. Crozier, C. Encarnacion, K. Hancock, M. J. Messing, K. A. Boehm, A. Williams, D. Ilegbodu, L. AsmarTenerie

14、llo M, et al. Presented at ASCO Annual Meeting 2007; Abstract 5525研討目的和規(guī)范研討目的和規(guī)范主要目的:總有效率 次要目的:PFSOSQOL平安性和毒性Teneriello M, et al. Presented at ASCO Annual Meeting 2007; Abstract 5525主要入組規(guī)范主要入組規(guī)范組織學(xué)或細(xì)胞學(xué)診斷的卵巢上皮癌、輸卵管癌或腹膜癌組織學(xué)或細(xì)胞學(xué)診斷的卵巢上皮癌、輸卵管癌或腹膜癌 任何期別，假設(shè)是任何期別，假設(shè)是I期，那么要求期，那么要求2-3級(jí)級(jí)RECIST規(guī)范可丈量的病灶，在無可丈量病灶的

15、情況下，規(guī)范可丈量的病灶，在無可丈量病灶的情況下，CA-125升高升高70曾接受鉑類為主方案的化療曾接受鉑類為主方案的化療鉑類治療敏感鉑類為主方案化療后無治療時(shí)間長于鉑類治療敏感鉑類為主方案化療后無治療時(shí)間長于6個(gè)月個(gè)月)ECOG 評(píng)分評(píng)分 (PS) 0-2假設(shè)有周圍神經(jīng)病變，級(jí)別低于假設(shè)有周圍神經(jīng)病變，級(jí)別低于1級(jí)級(jí)Teneriello M, et al. Presented at ASCO Annual Meeting 2007; Abstract 5525主要排除規(guī)范主要排除規(guī)范初次治療的初次治療的I期期1級(jí)患者級(jí)患者未接受過化療未接受過化療接受過接受過1個(gè)以上方案化療，或所用過的方案不

16、是鉑類為主的個(gè)以上方案化療，或所用過的方案不是鉑類為主的方案方案非上皮性腫瘤非上皮性腫瘤無可丈量病灶且無可丈量病灶且 CA-125 70入組入組6個(gè)月內(nèi)接受了紫杉類藥物的治療或曾運(yùn)用過白蛋白結(jié)個(gè)月內(nèi)接受了紫杉類藥物的治療或曾運(yùn)用過白蛋白結(jié)合型紫杉醇合型紫杉醇Teneriello M, et al. Presented at ASCO Annual Meeting 2007; Abstract 5525治療方案治療方案經(jīng)治醫(yī)生決議能否運(yùn)用預(yù)防用藥經(jīng)治醫(yī)生決議能否運(yùn)用預(yù)防用藥患者在每周期的第患者在每周期的第1天運(yùn)用白蛋白結(jié)合型紫杉醇天運(yùn)用白蛋白結(jié)合型紫杉醇 260 mg/m2 白蛋白結(jié)白蛋白結(jié)合型

17、紫杉醇，合型紫杉醇，30分鐘內(nèi)靜注，分鐘內(nèi)靜注，21天為天為1周期周期患者每患者每3周接受治療直到已證明為進(jìn)展或不可耐受的毒性或治療已達(dá)周接受治療直到已證明為進(jìn)展或不可耐受的毒性或治療已達(dá)6周期周期對(duì)于只需對(duì)于只需CA125升高無可丈量病灶的患者，在進(jìn)展療效評(píng)價(jià)之前，由升高無可丈量病灶的患者，在進(jìn)展療效評(píng)價(jià)之前，由經(jīng)治醫(yī)生決議治療的周期數(shù)，最多治療經(jīng)治醫(yī)生決議治療的周期數(shù)，最多治療3周期周期治療達(dá)治療達(dá)CR的患者，由經(jīng)治醫(yī)生決議能否再打兩個(gè)周期。因此，的患者，由經(jīng)治醫(yī)生決議能否再打兩個(gè)周期。因此，CR的的患者能夠接受最多患者能夠接受最多8個(gè)周期的化療個(gè)周期的化療Teneriello M, et

18、 al. Presented at ASCO Annual Meeting 2007; Abstract 5525患者的特征患者的特征入組患者數(shù)入組患者數(shù)47年齡年齡 (歲歲)范圍范圍65.442 84人數(shù)人數(shù)百分比百分比種族種族白種人白種人黑人黑人西班牙人西班牙人亞裔亞裔印度人印度人41131187.22.16.42.12.1ECOG 評(píng)分評(píng)分0138980.819.2既往治療既往治療化療間歇期化療間歇期 12 months化療間歇期化療間歇期 12 months手術(shù)手術(shù)4344491.58.593.6原發(fā)病原發(fā)病卵巢上皮癌卵巢上皮癌輸卵管癌輸卵管癌腹膜癌腹膜癌371978.72.119.2

19、組織學(xué)級(jí)別組織學(xué)級(jí)別GX (不能評(píng)價(jià)不能評(píng)價(jià))G1 (分化良好分化良好)G2 (中度分化中度分化)G3 (分化差分化差)丟失丟失/不清不清14923102.18.519.248.921.3Teneriello M, et al. Presented at ASCO Annual Meeting 2007; Abstract 5525結(jié)果結(jié)果符合條件的/治療的患者總數(shù)44N (%)95% CI最好的療效完全緩解完全緩解部分緩解部分緩解穩(wěn)定穩(wěn)定SD 6個(gè)月個(gè)月SD 6個(gè)月個(gè)月進(jìn)展進(jìn)展臨床受益臨床受益不可評(píng)價(jià)不可評(píng)價(jià)14 (31.8%)14 (31.8%)14 (31.8%)682 (4.5%)34

20、 (77.3%)3(18.1 45.6)(18.1 45.6)(18.1 45.6)(0 10.7)起效時(shí)間 (月)中位中位范圍范圍1.8(0.6 3.4)療效持續(xù)時(shí)間（月 )中位中位范圍范圍95% CI6.5(2.7 13.2)(6.6 N/A)Teneriello M, et al. Presented at ASCO Annual Meeting 2007; Abstract 5525最好療效最好療效符合條件/治療的患者總數(shù): 44RECIST測(cè)量*CA-125值 RECIST測(cè)量和 CA-125值完全緩解167部分緩解437穩(wěn)定（SD)527SD 6 months303SD 50%SD: 腫瘤減少腫瘤減少50% 或或 增大增大25% CA-125值丈