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1、卵巢癌化療新進(jìn)展The state of the art in chemotherapy for ovarian cancers,復(fù)旦大學(xué)附屬腫瘤醫(yī)院婦瘤科,女性生殖道腫瘤: 全世界統(tǒng)計1,,Ferlay et al. GLOBOCAN 2000 IARC, WHO 2001 (www.dep.iarc.fr),,Women,發(fā)病率 32%Breast 12%Lung 2001/, 2004.,,卵巢癌可認(rèn)為是一種慢性疾病,早期卵巢癌: FIGO I and II,全面的分期剖腹探查術(shù) 經(jīng)腹全子宮/雙側(cè)卵巢輸卵管切除 (TAH/BSO) 大網(wǎng)膜切除 淋巴結(jié)切除術(shù)（dissection） 腹膜和

2、膈膜活檢（ biopsies） 細(xì)胞學(xué)檢查 高危 vs 低危早期卵巢癌,Staging classifications and clinical practice guidelines of gynaecologic cancers. www.figo.org,早期卵巢癌,Medical Oncology: A comprehensive review. textbook,,,低危,高危,(510% 復(fù)發(fā)率),(3040% 復(fù)發(fā)率),Stage IA or IB,Stage IC,Grade 1 (or 2),Grade 3 Clear cell cancer,,,高危早期卵巢癌,Young

3、SGO 2003 2. Young RC. Semin Oncol 27 (3):8-10., 2000 3. ICON-1, EORTC-ACTION: J Natnl Can Inst. Vol. 95, No. 2, January 15, 2003 4. Mannel et al. GOG-175 protocol, www.cancernet.nci.nih.gov,,,GOG1571,2,輔助化療的隨機(jī)臨床試驗(yàn):3 vs 6 療程紫杉醇 + 卡鉑,結(jié)果 6個療程 進(jìn)展危險性降低了33% 生存率無改善,Action 淋巴結(jié)陰性;鏡下腹腔種植 B腹腔種植灶 2 cm; 淋巴結(jié)陰性 C腹

4、腔種植灶 2 cm 和/或陽性腹膜后淋巴結(jié)或腹股溝 IV遠(yuǎn)處轉(zhuǎn)移,Medical Oncology: A comprehensive review. textbook,準(zhǔn)確全面分期依據(jù)手術(shù)探查和 病理組織學(xué)、細(xì)胞學(xué)檢查 根據(jù)腹腔內(nèi)轉(zhuǎn)移灶的大小對III期再分為IIIa、IIIb、IIIc 腹膜后淋巴結(jié)轉(zhuǎn)移影響分期 肝表面和肝實(shí)質(zhì)轉(zhuǎn)移分屬III期和IV期,Stage I: 局限于卵巢 Stage II: 局限于盆腔 Stage III: 局限于腹腔 Stage IV: 遠(yuǎn)處轉(zhuǎn)移,,,,晚期卵巢癌：關(guān)鍵臨床實(shí)驗(yàn)1,GOG 1111 and OV-102 Cisplatin + paclitaxel

5、vs cisplatin + cyclophosphamide Improved survival and progression-free survival withcisplatin + paclitaxel GOG 1323 Cisplatin vs paclitaxel vs cisplatin + paclitaxel No statistaical difference in overall survival ICON-34 Carboplatin + paclitaxel vs carboplatin or CAP(cyclophosphamide + doxorubicin +

6、 cisplatin) No statistical difference in survival GOG 1585; AGO-OVAR6 Carboplatin + paclitaxel preferred combination overcisplatin + paclitaxel,1.McGuire WP et al. N Engl J Med 1996, 334:1-84.ICON Group. Lancet 2002, 360:505-515 2.Piccart M et al. Int J Gyn Cancer 2003, 13 (suppl 2), 144-1485. Ozols

7、 RF et al. J Clin Oncol 2003; 21:3194-3200 3.Muggia F et al. J Clin Oncol 2000, 18:106-1156.du Bois et al. J Natl Cancer Inst. 2003 Sep 3;95(17):1320-9,,,晚期卵巢癌: 關(guān)鍵臨床實(shí)驗(yàn)2,ICON-5-GOG182 （2006） Carboplatin + paclitaxel vs Gemcitabin triplet vs Doxil Triplet vs Topotecan duble + TP vs Gemcitabin dublet +

8、 TP(cyclophosphamide + doxorubicin + cisplatin) No statistical difference in survival GOG 172 （2006） cisplatin + paclitaxel iv/ip preferred combination overcisplatin + paclitaxel iv JGOG （2009） Carboplatin （d1）+ paclitaxel 80mg weekly perferred Carboplatin + paclitaxel,Armstrong D, et al. N Engl J M

9、ed 2006;354:34-43 .Isonishi S, et al. the Lancet 2009; 374:1331-38,TP方案成為晚期卵巢癌一線化療的“標(biāo)準(zhǔn)”,19,,1996,2000,,GOG111 (N=410)-期,環(huán)磷酰胺750mg/m2 順鉑75mg/m2,泰素35mg/m2(24h) 順鉑75mg/m2,VS,ORR: 73% 60% p=0.01,CR: 51% 31% p=0.01,PFS: 18mo 13mo

10、控,OV10 (N=688)-期,環(huán)磷酰胺750mg/m2 順鉑75mg/m2,泰素175mg/m2(3h) 順鉑75mg/m2,ORR: 77% 66% p=0.01,CR: 50% 36% p=0.01,PFS: 16.6mo 12mo p=0.0005,OS: 35mo 25mo p=0.0016,毒性: 泰素/順鉑組有較多的血液學(xué)毒性和神經(jīng)毒性，但毒性可控,VS,J Natl Cancer Inst 2000;92:699708,McGuire, et al. N Engl J Med 1996 334:1-6,GOG158: Ovarian (optimal

11、III),,Cisplatin 75 mg/m2 Paclitaxel 135 mg/m2 (24 h),,Carboplatin AUC 7.5 Paclitaxel 175 mg/m2 (3 h),Epithelial Ovarian Cancer Optimal Stage III No prior therapy Elective Second-Look Non-Inferiority Design,,,,Open:03-Apr-95 Closed:26-Jan-98 Accrual:792 pts (evaluable),I,,II,,Ozols, et al. Proc J Cli

12、n Oncol 21:3194, 2003,GOG158: Ovarian (optimal III),,CDDP-Paclitaxel (24-h) (n = 400) median 48.8 m,,,Carbo-Paclitaxel (3-h) (n = 392) median 56.7 m,Adjusted Cox analysis HR 0.86 (95% CI 0.71 1.04),Ozols, et al. Proc J Clin Oncol 21:3194, 2003,56.7 vs 48.8 m = 7.9 m,晚期卵巢癌的化療,總之: 手術(shù)和化療后約 75% 患者臨床完全緩解

13、（CCR）， 但復(fù)發(fā)率 50% 長期生存率 20 25%,提高療效的可能對策,引入更有效的方案 紫杉醇 / 卡鉑 + 新藥 腹腔化療 增加劑量強(qiáng)度 新的細(xì)胞毒性藥物 分子靶向治療 對復(fù)發(fā)癌更有效的治療 發(fā)明有效的維持治療,Ozols, Seminars in Oncology, vol 29; Suppl 1 (Feb) 2002: 32-42.,提高初治卵巢癌化療療效：三藥聯(lián)合化療,標(biāo)準(zhǔn)治療PC + X,GOG0182-ICON5,比較五種方案治療晚期卵巢上皮癌或原發(fā)性腹膜癌的III期隨機(jī)臨床試驗(yàn),25,Michael A Bookman, MD Fox Chase Cancer Cente

14、r Philadelphia, PA,Proc ASCO 2005:Abstract 5002,,GOG0182-ICON5,26,GOG0182-ICON5: 無進(jìn)展生存,Median PFS and HR (95% CI) 16.1 1.000 16.4 0.990 (0.884-1.107) 16.4 0.998 (0.891-1.117) 15.3 1.094 (0.979-1.224) 15.4 1.052 (0.940-1.176),GOG0182-ICON5: 總生存,Median OS and HR (95% CI) 40.0 1.000 40.4 0.978 (

15、0.838-1.141) 42.8 0.972 (0.832-1.136) 39.1 1.068 (0.918-1.244) 40.2 1.035 (0.888-1.206),GOG0182-ICON5： 結(jié)論,加入第三種細(xì)胞毒性藥物增加了血液學(xué)毒性，但是這種毒性是可控制的 在所有評價的方案中，加入第三種細(xì)胞毒藥物不能改善患者預(yù)后（包括無進(jìn)展生存和總生存）,29,,Proc ASCO 2005:Abstract 5002,IV IP,提高初治卵巢癌化療療效：改變用途徑,GOG172,31,,Cisplatin 75 mg/m2 Paclitaxel 135 mg/m2 (24 h),,C

16、isplatin 100 mg/m2 IP d1 Paclitaxel 135 mg/m2 (24 h) IV d1 Paclitaxel 60 mg/m2 IP d8,上皮性卵巢癌 III期 滿意減滅術(shù) 術(shù)前無治療 選擇性二探,,,,Open:23-Mar-98 Closed:29-Jan-01 Accrual:415 例 (可評價),I,,II,,Armstrong, et al. NEJM 354:34-43, 2006,GOG172: Ovarian (optimal III) IP vs. IV,,CDDP (IV) Paclitaxel (IV) (n = 210),,,CDDP

17、(IP) Paclitaxel (IP+IV) (n = 206),Armstrong, et al. NEJM 354:34-43, 2006,GOG 172,結(jié)論：靜脈內(nèi)紫杉醇聯(lián)合腹腔內(nèi)順鉑和紫杉醇可改善理想減滅術(shù)后 III期卵巢癌患者的生存率,33,3周療周療,提高初治卵巢癌化療療效：增加用藥頻率,PC紫杉醇周療 vs 標(biāo)準(zhǔn)PT3周療 (JGOG ，2009),每周療：Paclitaxel 80mg d1, 8,15 Carboplatin AUC 6 d1 3周療：Paclitaxel 180mg d1 Carboplatin AUC 6 d1,Isonishi S,

18、 et al. the Lancet 2009; 374:1331-38,晚期卵巢癌化療,卡鉑和紫杉醇：卡鉑（AUC=56）紫杉醇(175mg/m2) 滴注 3小時，每3周重復(fù)，共68個療程(catrgory 1) 順鉑和紫杉醇：紫杉醇(135mg/m2) iv d1，DDP 100mg/m2 ip d2,紫杉醇(60mg/m2) ip d8,每3周重復(fù)，共68個療程(catrgory 1) 卡鉑和多西紫杉醇：卡鉑（AUC=56）多西紫杉醇(60-75mg/m2) 滴注 1小時，每3周重復(fù)，共68個療程(catrgory 1) 如對泰素過敏，可改用其他替代藥物（如：泰素帝，topotecan，

19、健擇，或脂質(zhì)體阿霉素）。 不能耐受靜脈化療者，可選用口服化療藥，如：VP-16。,舉例：Case 1,53歲，女性 表現(xiàn)為腹脹 無腹腔外腫瘤生長證據(jù) 腫瘤中等度大 實(shí)施活檢后患者被轉(zhuǎn)至婦科腫瘤醫(yī)師,舉例：Case 1,對此患者實(shí)施了滿意的細(xì)胞減滅術(shù). 殘留腫瘤最大直徑：1cm. 1枚腹主動脈旁淋巴結(jié)累及 病理：中分化漿液性乳頭狀癌 轉(zhuǎn)至尋求化療,,舉例：Case 1,我們的患者選擇腹腔化療 2個周期化療后她的CA125水平自122降至10 患者無癥狀，繼續(xù)接受了4個周期的化療 盆腔檢查、CT掃描、CA125結(jié)果均正常,新輔助化療與中間性細(xì)胞減滅術(shù),Neoadjuvant Chemotherap

20、y Interval Cytoreduction,中間性細(xì)胞減滅術(shù)（12th IGCS曼谷，2008）,隨機(jī)非劣性實(shí)驗(yàn)：718例IIIc-IV期卵巢癌 初次細(xì)胞減滅術(shù)化療6程 Vs 化療3程細(xì)胞減滅術(shù)化療3程 總生存率：29 m vs 30 m PFS: 12 m vs 12 m,Vergote et al. 12th biennial meeting of IGCS, Bangkok, Thailand,2008,,腸系膜根部轉(zhuǎn)移 肝實(shí)質(zhì)多發(fā)轉(zhuǎn)移,,,,,,,,,,,,,,上皮性卵巢癌：Epithelial Ovarian Cancer (EOC)100例患者的典型“結(jié)局”,Early st

21、age (I-II),Advanced stage (III-IV),Clinical partial response(cPR), Stable disease(SD), Progression,Relapse / Progression,Clinical complete response (cCR),25,75,8,40,35,Pathologic partial Response(pPR),Pathologic complete Response(pCR),16,24,Relapse,2nd3rd line therapy,8,73,,FIGO annual report on tre

22、atments of gynecological cancers Editor: Pecorelli S. Intern J Gynecol 95:132030,約 25% 患者于一線TC(paclitaxel+Carb.)治療后 6-12個月復(fù)發(fā),約 50% 患者于一線TC治療后 12個月復(fù)發(fā),存在的相關(guān)問題大多數(shù)(55%) 晚期患者將會出現(xiàn)鉑類敏感性復(fù)發(fā),,,,,,,,無治療間期,,,,,,,,,,0 6,,,7 12,,13 18, 18,0,20,40,60,80,100,距前次治療的時間（月）,有效率 (%),Blackledge, et al. Br J Cancer. 1989;

23、59:650-653.,二線化療的目標(biāo),分類 目標(biāo) 治療無效 緩解 ( 6, 12 個月) 治愈?,,,,對鉑類敏感的卵巢癌,兩藥聯(lián)合化療能否成為對鉑類敏感的復(fù)發(fā)性卵巢癌患者的治療標(biāo)準(zhǔn)？,,對鉑類敏感的復(fù)發(fā)性卵巢癌單藥有效率 累積總有效率（OR）,du Bois A et al. 2000 Geburtsh Frauenheilk 2000; 60:41-58,但是, 這個問題在一個RCT即可解決!,,Pfisterer et al. J Clin Oncol 2006;24(29):4699-4707.,健擇/卡鉑治療復(fù)發(fā)卵巢癌的III期臨床試驗(yàn),健擇/卡鉑治療復(fù)發(fā)卵巢癌的

24、III期臨床試驗(yàn): PFS,,,,,,,,,卡鉑組178例162例進(jìn)展事件；健擇/卡鉑組178例163例進(jìn)展事件,Pfisterer et al. J Clin Oncol 2006;24(29):4699-4707.,鉑類敏感的復(fù)發(fā)卵巢癌患者 健擇聯(lián)合卡鉑方案顯著延長PFS，提高緩解率，且未降低生活質(zhì)量1 健擇聯(lián)合卡鉑快速緩解癥狀，并明顯改善生活質(zhì)量2,1Pfisterer et al. J Clin Oncol 2006;24(29):4699. 2Pfisterer et al. Int J Gynecol Cancer 2005;15(Suppl 1):36-41.,健擇/卡鉑治療復(fù)發(fā)

25、卵巢癌的III期臨床試驗(yàn),,各個方案的毒副作用不同： 卡鉑-紫杉醇：神經(jīng)毒性 卡鉑-多西紫杉醇：血液性毒性 卡鉑-吉西他濱：血液性毒性 順鉑-吉西他濱：血液性毒性,鉑類耐藥復(fù)發(fā)性卵巢癌治療模式:,手術(shù) few selected pts. (e.g. bowel obstruction),內(nèi)分泌 TX Selected pts., rather 3rd/4th line ?,支持治療 every pt. as needed,放療 few selected pts.,心理-社會支持 every pt. as needed,“新藥“ only in clinical trials,非鉑單藥 Tx,非

26、鉑聯(lián)合 Tx,鉑類為主治療 mainly pt-sensitive ROC,From Dr. Andreas du Bois,,對鉑類耐藥卵巢癌,選擇哪種非鉑類？ 單藥 聯(lián)合 或改變用藥途徑？ 或改變用藥方案？,,有效率 隨機(jī)臨床試驗(yàn)，0 6個月,紫杉醇 1,4 n = 90,拓泊替康 1,2,4 n = 259,楷萊 3 n = 130,奧沙利鉑 4 n = 132,1 ten Bokkel JCO 1997 2 Gore EJC 2002 3 GordonJCO 2001 4 Piccart JCO

27、 2000,%,有效率 隨機(jī)臨床試驗(yàn)， 6個月,紫杉醇 1,4 n = 90,拓泊替康 1,2,4 n = 259,楷萊 3 n = 109,奧沙利鉑 4 n = 132,1 ten Bokkel JCO 1997 2 Gore EJC 2002 3 GordonJCO 2001 4 Piccart JCO 2000,%,,What is the Evidence?,Randomised Studies in Recurrent OC: Studies Pts. mono- vs. mono chemo

28、therapy 10 2.195 mono: schedule/dose/application 7 1.614 mono- vs. endocrine therapy 2 303 endocrine vs. endocrine therapy 2 106 combination vs. combination 2 107 mono vs. combination* 14 3.499 all: 37 7.924 * Including 1 trial with multiple regimens according to testing; most other trials in pt

29、s. with platinum sensitive relapse,,,,R,,,,,Paclitaxel 175 mg/m 3h q21,Paclitaxel 175 mg/m Epirubicin 80 mg/m q21,Buda A 2004, Br J Cancer,106 pts. 12 mos.,106 pts.,results: OR 47% vs. 37% (combi), PFS 6 vs. 6 mos. OS 14 vs. 12 mos. (n.s.),R,,,,,Topotecan 1.25 mg/m d1-5 q21,Topotecan 1.0 mg/m d1-5 E

30、toposid 50 mg po d 6-12 q21,Sehouli J 2008, JCO,178 pts.,177 pts.,results: OR 36% (TE) vs. 32% (TG) vs. 28 % (Topo) mean PFS 15 vs. 13 vs. 13 months (n.s.) mean OS 23 vs. 18 vs. 24 months (n.s.),,Topotecan 0.5 - 0.75 mg/m d1-5 Gemcitabine 800 mg/m d1 + 600 mg/m d8 q21,app. 20% refractory 41% 12

31、Mon.,147 pts.,mono vs. combination chemotherapy in refractory recurrent OC,,Trabectedin+PLD 4.0 mos,PLD 3.7 mos,PFS events: 163 HR: 0.95 (0.70-1.30) P = 0.7540 by courtesy of BJ Monk et al (Email: bjmonkuci.edu),mono vs. combination chemotherapy in refractory recurrent OC,R,,,,,Doxil/Caelyx (PLD) 50

32、 mg/m q28,Trabectedin 1.1 mg/m q 21 + Doxil/Caelyx (PLD) 30 mg/m q28,BJ Monk et all , ESMO 2008,118 pts.,113 pts.,results: OR 12,2% vs 13,4% (combi; n.s.), PFS/OS n.s.,,鉑類耐藥復(fù)發(fā)性卵巢癌治療模式:,手術(shù) few selected pts. (e.g. bowel obstruction),內(nèi)分泌 TX Selected pts., rather 3rd/4th line ?,支持治療 every pt. as needed,

33、放療 few selected pts.,心理-社會支持 every pt. as needed,“新藥“ only in clinical trials,非鉑單藥 Tx,目前尚無足夠證據(jù)支持 非鉑聯(lián)合 Tx,鉑類為主治療 mainly pt-sensitive ROC,From Dr. Andreas du Bois,,,What is the Evidence?,Randomised Studies in Recurrent OC: Studies Pts. mono- vs. mono chemotherapy 10 2.195 mono: schedule/dose/applicati

34、on 7 1.614 mono- vs. endocrine therapy 2 303 endocrine vs. endocrine therapy 2 106 combination vs. combination 2 107 mono vs. combination* 14 3.499 all: 37 7.924 * Including 1 trial with multiple regimens according to testing; most other trials in pts. with platinum sensitive relapse,,,Weekly Pa

35、clitaxel,65,復(fù)發(fā)或耐藥的卵巢癌癌患者,泰素80mg/m2, 每周給藥，連續(xù)3周，休息一周，至少兩周期。,,Weekly Paclitaxel （80 mg/m2/周）,用于對TP方案無反應(yīng)或耐藥的病例 RR Markman25% Kaern 56% Kita25-56% 毒性主要為可耐受的神經(jīng)毒性 ______________________ J Clin Oncol 20:2365, 2002 Eur J Gynecol Oncol 23:383, 2002 Gynecol Oncol 92:813, 2004,66,,R,,,,,T

36、opotecan 1,5 mg/m iv d1-5 q21,Caelyx 50 mg/m iv q28,Gordon 2001, J Clin Oncol 2004, Gynecol Oncol,235 pts. 55% Pt.-refractory, 70% prior taxans,239 pts.,Results platinum refractory subgroup:Caelyx (130)Topotecan (124) p-value PFS (weeks, median) 9,1 13,1 0.733 OS (weeks, median) 36 41 0.455 G3

37、/4 toxicity (all pts.;%) Neutropenia 12 77 < 0.001 Anemia 5 28 < 0.001 Thrombocytopenia 1 34 < 0.001 Leukopenia 10 50 < 0.001 Treatment-related sepsis 0 4 < 0.001 Alopecia (all grades) 16 49 0.007 Hand-Foot-Syndrom 23 0 < 0.001 Stomatitis 8 0.4 < 0.001,mono vs. mono chemotherapy in recu

38、rrent (mostly) refractory OC - RCTs,,,,,R,,,,,Gemcitabine 1000 mg/m d1+8 q21,Caelyx 50 mg/m d1 q28,Mutch, JCO 2007,99 pts.,96 pts.,Results:,,,mono vs. mono chemotherapy in recurrent (mostly) refractory OC - RCTs,66 pts.,64 pts.,*Statistically significant.,健擇vs.聚乙二醇脂質(zhì)體阿霉素治療鉑類耐藥的卵巢癌的III期臨床試驗(yàn),研究結(jié)論： 健擇可

39、替代聚乙二醇脂質(zhì)體阿霉素治療鉑類耐藥的卵巢癌患者,Mutch DG, et al. J Clin Oncol 2007;25(19):2811-2819.,Results: OR 16% vs. 18% (Gem), OR duration 18 vs. 17 (Gem) weeks ; n.s. QoL advantage for caelyx in 2 of 4 time points (p < 0.05),R,,,,,Gemcitabine 1000 mg/m d1,8, 15 q28,Caelyx 40 mg/m d1 q28,Mito-3 G Ferrandina et al

40、JCO 2008,77 pts. 100% platinum-taxan, TFI < 12 mos. (57% < 6 mos.),76 pts.,mono vs. mono chemotherapy in recurrent (mostly) refractory OC - RCTs,,,鉑類耐藥復(fù)發(fā)性卵巢癌治療模式:,手術(shù) few selected pts. (e.g. bowel obstruction),內(nèi)分泌 TX Selected pts., rather 3rd/4th line ?,支持治療 every pt. as needed,放療 few selected pts.,心

41、理-社會支持 every pt. as needed,“新藥“ only in clinical trials,首選 非鉑單藥： Caelyx Topotecan Gemcitabine,目前尚無足夠證據(jù)支持 非鉑聯(lián)合 Tx,鉑類為主治療 mainly pt-sensitive ROC,From Dr. Andreas du Bois,,,二線治療,一線治療,一線治療,三線治療,,,12 個月,3 個月,3 個月,STOP,STOP,二線治療,3 個月,3 個月,卵巢癌終止治療： London Royal Marsden Hospital 指南,Maintenance（維持） Prolonge

42、d administration of treatment 延長治療 Treatment until progression 治療至進(jìn)展 Consolidation（鞏固） A defined therapy following a responseto initial treatment 首次治療有效后，接著同樣的治療,定義：Definitions,,,鞏固/維持治療 隨機(jī)臨床試驗(yàn)（RCT） （i.v. ）,1. Scarfone ASCO 2002 abstract book: 2. Shroeder IGCS 2004 Abstr 567: 3. MITO-1 J Clin Oncol.

43、 2004 Jul 1; 22(13):263542: 4. Cure J of Clin Oncol, 2004 ASCO Vol 22, No 14S (July 15 Supplement), 2004; 5006: 5. Markman JCO, Vol 21, No 13 (July 1) 2003; 24602465,鞏固化療,Markman的期臨床研究： 兩組PFS相差7個月，OS無差異,277 例卵巢癌患者經(jīng)過手術(shù)后及TP 聯(lián)合化療達(dá)到完全緩解,R,Taxol 175 mg/ m2 3小時滴 注，每月1 次，共3個月,Taxol 175 mg/ m2 3 小時滴 注，每月1

44、 次，共12個月,Markman M et al. Gynecol Oncol 2002; 84(3):79,,,卵巢癌: 生物靶向治療,獨(dú)特腹腔上皮和Mllerian上皮 Specialized relationship; spread via implantation Frequent production of ascites, associated with VEGF Negative immunoregulation (VEGF, IL-10, IL-6, IL-12, APC) 生長因子受體 EGF-R frequently expressed, mutations uncommo

45、n, frequency of overexpression variable HER2/neu frequently expressed, high-level overexpression <15%, gene amplification uncommon ER/PR/AR frequently expressed, variable functionality Other receptors less well characterized 生長因子產(chǎn)物 Frequent high-level expression of VEGF Increased expression of IL10,

46、 IL6, TNF, TGF,New trials: GOG,Epithelial Ovarian Cancer and primary peritoneal cancer No prior chemotherapy and suboptimal 1cm disease,,舉例：Case 1,該患者術(shù)后每3月隨訪Ca125和超聲檢查 在術(shù)后19個月時發(fā)現(xiàn) Ca125逐漸上升 16，26，38，48 iu/ml 無任何癥狀 和體征 再來尋求治療,,,,,,,,,,,,,過早,治療 PS評分 0 - 1,過遲 PS評分 3 - 4,血清CA125,治療復(fù)發(fā)性卵巢癌,,腫瘤體積,Gore

47、2001, ASCO 教育手冊,,卵巢癌診斷：細(xì)胞減滅術(shù) 化療 隨訪： Ca125 ？ 立即化療？ 出現(xiàn)癥狀或體征后再化療？,卵巢癌：CA125監(jiān)測 （abs#1）,,,,患者登記 每3個月進(jìn)行CA125的檢測（檢測結(jié)果對醫(yī)生和患者保持盲態(tài)）,,研究設(shè)計,卵巢癌患者在經(jīng)過一線以鉑類為基礎(chǔ)的化療后，達(dá)到臨床完全緩解，CA125水平正常,,,當(dāng)兩次CA125水平超過正常上限 隨機(jī)分組,,,即刻治療組 醫(yī)生和患者被告知,延遲治療組 醫(yī)生不被告知，直至復(fù)發(fā)開始治療,,,,,卵巢癌：CA125監(jiān)測 （abs#1）,研究結(jié)果：總生存期,卵巢癌：CA125監(jiān)測 （abs#1）,結(jié)論 ：,與延遲治療組相比，

48、僅根據(jù)CA125升高而進(jìn)行早期治療： 二線化療平均提早4.8個月 三線化療平均提早4.6個月 早期治療沒有延長總生存期 HR1.00, 95%CI 0.82-1.22, p=0.98 2年生存率的絕對差異為-0.1%(95%CI -6.8, 6.3%) 早期化療沒有提高生活質(zhì)量（-1.7月）,卵巢癌：CA125監(jiān)測 （abs#1）,,小結(jié),早期可用3-6程PC化療（IA-IB ：G1-2可觀察隨訪） 晚期標(biāo)準(zhǔn)治療：PC 6-8程，（IP；紫杉醇周療 能提高療效，但毒副作用較大） 新輔助化療可用于難以切除術(shù)病例，但不能提高生存率 鉑敏感復(fù)發(fā)癌可繼續(xù)用鉑類聯(lián)合治療，但應(yīng)考慮不同藥物的副作用（PC, CD, CG, cis-PG） 鉑耐藥者應(yīng)選用非鉑類單藥：（P 周療，T, G, D,) 鞏固/維持治療的可以提高FPS，但不能提高OS 靶向治療是今后發(fā)展方向(貝伐單抗-化療) 據(jù)Ca125升高立即化療，不能提高生存率和生活質(zhì)量,,謝 謝,