乳腺癌化療進(jìn)展-PPT精選課件

1、乳腺癌化療進(jìn)展紫杉醇藥物在乳腺癌中的應(yīng)用乳腺癌流行病學(xué) 發(fā)病率在逐年上升 張忠清 乳腺癌當(dāng)前流行趨勢(shì)分析 中國(guó)腫瘤 2000 9（10）：454 年份 全球 我國(guó)新發(fā)例數(shù)（萬(wàn)）發(fā)病率（1/10萬(wàn)）新發(fā)例數(shù)（萬(wàn)）發(fā)病率（1/10萬(wàn)）197554.123.75.412.3198057.225.83.16.4198571.929.86.713.1199079.530.36.111.0乳腺癌流行病學(xué) 死亡率國(guó)家死亡率（1/10萬(wàn)）國(guó)家死亡率（1/10萬(wàn)）國(guó)家死亡率（1/10萬(wàn)）丹麥26.4意大利20.7希臘15.9荷蘭25.3澳大利亞20.2保加利亞14.8英國(guó)25.1法國(guó)19.7秘魯14.2瑞士22

2、.6西班牙17.4哈薩克斯坦12.8德國(guó)22.1葡萄牙17.4哥倫比亞9.1奧地利21.8瑞典17.3墨西哥8.9捷克21.6波蘭16.3日本7.1阿根廷21.2俄羅斯16.3中國(guó)城區(qū)6.2加拿大20.9羅馬尼亞16.0美國(guó)20.7匈牙利15.9張忠清 乳腺癌當(dāng)前流行趨勢(shì)分析 中國(guó)腫瘤 2000 9（10）：454死亡率下降的原因生活方式改變?cè)缙谠\斷率提高治療方法改進(jìn)張忠清 乳腺癌當(dāng)前流行趨勢(shì)分析 中國(guó)腫瘤 2000 9（10）：454乳腺癌在常見(jiàn)腫瘤中生存率最高分期20年生存率（%）原位95.8I 期96.8II a75.4II b 71.7II c70.1II d59.6III 40.3張

3、忠清 乳腺癌當(dāng)前流行趨勢(shì)分析 中國(guó)腫瘤 2000 9（10）：454預(yù)后和預(yù)測(cè)因素腫瘤大小分化程度組織侵犯情況淋巴結(jié)轉(zhuǎn)移情況（淋巴）結(jié)外轉(zhuǎn)移情況腫瘤倍增速率ERPgRErb B-2EGRF Dr. Ann ThorThe 2nd International Breast Cancer International Research Group Conference ER和PgR對(duì)腫瘤復(fù)發(fā)有預(yù)示作用ER(+)與()：5年內(nèi)生存率差別較為顯著 5-10年以后兩者差別不大 Dr. Ann ThorThe 2nd International Breast Cancer International Res

4、earch Group Conference erbB-2對(duì)侵襲性導(dǎo)管癌的復(fù)發(fā)有預(yù)示作用erbB-2（+）高劑量化療 敏感 （-）高劑量化療 不敏感erbB-2（+）對(duì)含蒽環(huán)霉素的化療方案療效更好erbB-2（+）對(duì)CMF方案的受益有限erbB-2（+）+EGRF（+）預(yù)后不良 Dr. Ann ThorThe 2nd International Breast Cancer International Research Group Conference 乳腺癌化療進(jìn)展乳腺癌化療回顧20世紀(jì)70年代：環(huán)磷酰胺、甲氨蝶呤、氟脲嘧啶等非蒽環(huán)類(lèi)藥物為主 20世紀(jì)80年代：阿霉素、表阿霉素等蒽環(huán)類(lèi)聯(lián)合化療

5、為代表 20世紀(jì)90年代：紫杉醇和多西紫杉醇等紫杉類(lèi)藥物被稱(chēng)為腫瘤化療的重大突破江澤飛 紫杉類(lèi)藥物在乳腺癌化療中的地位和臨床研究進(jìn)展 中國(guó)醫(yī)學(xué)論壇報(bào)網(wǎng)絡(luò)版866期當(dāng)代觀(guān)點(diǎn)紫杉類(lèi)蒽環(huán)類(lèi)聯(lián)合化療是治療乳腺癌的最有效方案之一 江澤飛 紫杉類(lèi)藥物在乳腺癌化療中的地位和臨床研究進(jìn)展 中國(guó)醫(yī)學(xué)論壇報(bào)網(wǎng)絡(luò)版866期紫杉醇 vs CMFP目的：比較紫杉醇單藥治療和非蒽環(huán)類(lèi)聯(lián)合方案一線(xiàn)化療對(duì)轉(zhuǎn)移性乳腺癌的效果CMFP：環(huán)磷酰胺+氨甲喋呤+5-氟脲嘧啶+三苯氧胺Bishop JF. Initial paclitaxel improves outcome compared with CMFP combination

6、 chemotherapy as front-line therapy in untreated metastatic breast cancer. J Clin Oncol. 2019 Aug;17(8):2355試驗(yàn)設(shè)計(jì)Bishop JF. Initial paclitaxel improves outcome compared with CMFP combination chemotherapy as front-line therapy in untreated metastatic breast cancer. J Clin Oncol. 2019 Aug;17(8):2355結(jié)果紫

7、杉醇（n=107）CMFP（n=102）P值有效率完全+部分29%35%0.37腫瘤無(wú)進(jìn)展生存情況估測(cè)中位生存期(月)5.36.40.251年腫瘤無(wú)進(jìn)展存活率15%17%2年腫瘤無(wú)進(jìn)展存活率3%5%總生存情況估測(cè)中位生存期(月)17.313.90.0681年存活率61552年存活率3920Bishop JF. Initial paclitaxel improves outcome compared with CMFP combination chemotherapy as front-line therapy in untreated metastatic breast cancer. J C

8、lin Oncol. 2019 Aug;17(8):2355估測(cè)生存曲線(xiàn)Bishop JF. Initial paclitaxel improves outcome compared with CMFP combination chemotherapy as front-line therapy in untreated metastatic breast cancer. J Clin Oncol. 2019 Aug;17(8):2355生活質(zhì)量改變情況Bishop JF. Initial paclitaxel improves outcome compared with CMFP combi

9、nation chemotherapy as front-line therapy in untreated metastatic breast cancer. J Clin Oncol. 2019 Aug;17(8):2355結(jié)論紫杉醇 vs CMFP生存期更長(zhǎng)化療毒性更少生活質(zhì)量相似控制腫瘤進(jìn)展相似Bishop JF. Initial paclitaxel improves outcome compared with CMFP combination chemotherapy as front-line therapy in untreated metastatic breast canc

10、er. J Clin Oncol. 2019 Aug;17(8):2355紫杉醇單藥治療乳腺癌與其它常用化療方案比較（薈萃分析）方案對(duì)照結(jié)果阿霉素+環(huán)磷酰胺(AC)CMFP惡心、嘔吐、胃炎發(fā)生較高米托蒽醌CMFP對(duì)腫瘤控制欠佳紫杉醇CMFP生存期更長(zhǎng)，化療毒性更少StocklerThe 2nd International Breast CancerInternational Research Group Conference阿霉素 vs 紫杉醇 vs 聯(lián)合方案目的：比較阿霉素、紫杉醇及其聯(lián)合方案（AT）一線(xiàn)治療轉(zhuǎn)移性乳腺癌的效果Sledge GW. Phase III trial of dox

11、orubicin,paclitaxel,and the combination of doxorubicin and paclitaxel as front-line chemotherapy for metastatic breast cancer: an intergroup trial (E1193). J Clin Oncol. 2019 Feb 15;21(4):588 試驗(yàn)設(shè)計(jì)每三周重復(fù)一次，為一療程。阿霉素(A)紫杉醇(T)聯(lián)合方案(A+T)224人229人230人60 mg/m2 175 mg/m2 A：50mg/m2 T：150mg/m2Sledge GW. Phase II

12、I trial of doxorubicin,paclitaxel,and the combination of doxorubicin and paclitaxel as front-line chemotherapy for metastatic breast cancer: an intergroup trial (E1193). J Clin Oncol. 2019 Feb 15;21(4):588 治療有效率（CR+PR）A vs T P =0.84A vs AT P =0.07T vs AT P=0.04Sledge GW. Phase III trial of doxorubic

13、in,paclitaxel,and the combination of doxorubicin and paclitaxel as front-line chemotherapy for metastatic breast cancer: an intergroup trial (E1193). J Clin Oncol. 2019 Feb 15;21(4):588 腫瘤無(wú)進(jìn)展生存時(shí)間A vs T p=0.68A vs AT p=0.03T vs AT p=0.09Sledge GW. Phase III trial of doxorubicin,paclitaxel,and the com

14、bination of doxorubicin and paclitaxel as front-line chemotherapy for metastatic breast cancer: an intergroup trial (E1193). J Clin Oncol. 2019 Feb 15;21(4):588 中位生存期P=NSSledge GW. Phase III trial of doxorubicin,paclitaxel,and the combination of doxorubicin and paclitaxel as front-line chemotherapy

15、for metastatic breast cancer: an intergroup trial (E1193). J Clin Oncol. 2019 Feb 15;21(4):588 16周時(shí)生存質(zhì)量（QOL）比較P=NS分組A(n=136)T(n=150)A+T(n=165)治療前QOL107.5110.3111.016周時(shí)QOL105.8107.4108.0QOL改變-1.7-2.8-3.0Sledge GW. Phase III trial of doxorubicin,paclitaxel,and the combination of doxorubicin and paclit

16、axel as front-line chemotherapy for metastatic breast cancer: an intergroup trial (E1193). J Clin Oncol. 2019 Feb 15;21(4):588 結(jié)論阿霉素與紫杉醇治療活性相當(dāng)聯(lián)合化療方案在總體有效率和腫瘤無(wú)進(jìn)展時(shí)間較好聯(lián)合方案與單藥序貫治療的生存期和生活質(zhì)量相當(dāng)Sledge GW. Phase III trial of doxorubicin,paclitaxel,and the combination of doxorubicin and paclitaxel as front-li

17、ne chemotherapy for metastatic breast cancer: an intergroup trial (E1193). J Clin Oncol. 2019 Feb 15;21(4):588 阿霉素+紫杉醇增加用藥劑量是否會(huì)提高療效？Gianni：有效率94% CR40%Sparano ：有效率：53% 初治有效率：63% 缺點(diǎn)：充血性心衰Dr. George SledgeThe 2nd International Breast CancerInternational Research Group Conference表阿霉素+紫杉醇有效率40%-80%充血性心衰

18、發(fā)生較少Dr. George SledgeThe 2nd International Breast CancerInternational Research Group Conference多西紫杉醇 vs 阿霉素研究對(duì)象：接受過(guò)含烷化劑化療方案治療的轉(zhuǎn)移性乳腺癌患者方案多西紫杉醇阿霉素p治療人數(shù)161165劑量100mg/m275 g/m2有效率47.8%33.3%0.008腫瘤無(wú)進(jìn)展時(shí)間26周21周NS中位生存期15月14月NSChan S. Prospective randomized trial of docetaxel versus doxorubicin in patients w

19、ith metastatic breast cancer. The 303 Study Group. J Clin Oncol. 2019 Aug;17(8):2341 多西紫杉醇 vs 阿霉素 有效率優(yōu)勢(shì)比Chan S. Prospective randomized trial of docetaxel versus doxorubicin in patients with metastatic breast cancer. The 303 Study Group. J Clin Oncol. 2019 Aug;17(8):2341 多西紫杉醇 vs 阿霉素Kaplan-Meier治療有效率

20、曲線(xiàn)Chan S. Prospective randomized trial of docetaxel versus doxorubicin in patients with metastatic breast cancer. The 303 Study Group. J Clin Oncol. 2019 Aug;17(8):2341 多西紫杉醇 vs絲裂霉素+長(zhǎng)春花堿(MV)目的：比較多西紫杉醇與MV方案對(duì)經(jīng)蒽環(huán)類(lèi)藥物化療的轉(zhuǎn)移性乳腺癌的療效Nabholtz JM. Prospective randomized trial of docetaxel versus mitomycin plus

21、 vinblastine in patients with metastatic breast cancer progressing despite previous anthracycline-containing chemotherapy. 304 Study Group. J Clin Oncol. 2019 May;17(5):1413-24 化療方案多西紫杉醇MV治療人數(shù)203189劑量100 mg/m2 (3周一次)M:12 mg/m2 (6周一次)V:6 mg/m2 (3周一次)最大療程：103周Nabholtz JM. Prospective randomized trial

22、of docetaxel versus mitomycin plus vinblastine in patients with metastatic breast cancer progressing despite previous anthracycline-containing chemotherapy. 304 Study Group. J Clin Oncol. 2019 May;17(5):1413-24 有效率Nabholtz JM. Prospective randomized trial of docetaxel versus mitomycin plus vinblasti

23、ne in patients with metastatic breast cancer progressing despite previous anthracycline-containing chemotherapy. 304 Study Group. J Clin Oncol. 2019 May;17(5):1413-24 多西紫杉醇 vs MV有效率優(yōu)勢(shì)比Nabholtz JM. Prospective randomized trial of docetaxel versus mitomycin plus vinblastine in patients with metastatic

24、 breast cancer progressing despite previous anthracycline-containing chemotherapy. 304 Study Group. J Clin Oncol. 2019 May;17(5):1413-24 多西紫杉醇 vs MVKaplan-Meier生存率曲線(xiàn)Nabholtz JM. Prospective randomized trial of docetaxel versus mitomycin plus vinblastine in patients with metastatic breast cancer prog

25、ressing despite previous anthracycline-containing chemotherapy. 304 Study Group. J Clin Oncol. 2019 May;17(5):1413-24 多西紫杉醇聯(lián)合化療方案 (文獻(xiàn)回顧)有效率：57%-77%中位腫瘤進(jìn)展時(shí)間(TTP)：47-59周2年生存率：60%-67%毒性反應(yīng)： 以中性粒細(xì)胞減少癥及發(fā)熱為主 無(wú)致死性毒性反應(yīng)報(bào)道 可與阿霉素同時(shí)使用而不增加發(fā)生充血性心衰 的危險(xiǎn)Dr. NabholtzThe 2nd International Breast CancerInternational Res

26、earch Group ConferenceTrastuzumab 抗Her-2/neu人型單克隆抗體 協(xié)同作用：鉑劑、多西紫杉醇、放療相加作用：阿霉素、紫杉醇、環(huán)磷酰胺目前的研究表明最有效的聯(lián)合治療方案為Weekly Paclitalx /carboplatin with Herceptin.Dr. NabholtzThe 2nd International Breast CancerInternational Research Group Conference紫杉醇周劑量化療方案紫杉醇CR+PRCR+PR+ST總體評(píng)價(jià)22%63%一線(xiàn)治療26%77%二線(xiàn)治療22%61%三線(xiàn)治療15%49%有紫杉醇藥物應(yīng)用史16%38%無(wú)紫杉醇藥物應(yīng)用史24%