1、乳腺癌化療進展紫杉醇藥物在乳腺癌中的應用乳腺癌流行病學 發病率在逐年上升 張忠清 乳腺癌當前流行趨勢分析 中國腫瘤 2000 9（10）：454 年份 全球 我國新發例數（萬）發病率（1/10萬）新發例數（萬）發病率（1/10萬）197554.123.75.412.3198057.225.83.16.4198571.929.86.713.1199079.530.36.111.0乳腺癌流行病學 死亡率國家死亡率（1/10萬）國家死亡率（1/10萬）國家死亡率（1/10萬）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25.1法國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中國城區6.2加拿大20.9羅馬尼亞16.0美國20.7匈牙利15.9張忠清 乳腺癌當前流行趨勢分析 中國腫瘤 2000 9（10）：454死亡率下降的原因生活方式改變早期診斷率提高治療方法改進張忠清 乳腺癌當前流行趨勢分析 中國腫瘤 2000 9（10）：454乳腺癌在常見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 乳腺癌當前流行趨勢分析 中國腫瘤 2000 9（10）：454預后和預測因素腫瘤大小分化程度組織侵犯情況淋巴結轉移情況（淋巴）結外轉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對腫瘤復發有預示作用ER(+)與()：5年內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對侵襲性導管癌的復發有預示作用erbB-2（+）高劑量化療 敏感 （-）高劑量化療 不敏感erbB-2（+）對含蒽環霉素的化療方案療效更好erbB-2（+）對CMF方案的受益有限erbB-2（+）+EGRF（+）預后不良 Dr. Ann ThorThe 2nd International Breast Cancer International Research Group Conference 乳腺癌化療進展乳腺癌化療回顧20世紀70年代：環磷酰胺、甲氨蝶呤、氟脲嘧啶等非蒽環類藥物為主 20世紀80年代：阿霉素、表阿霉素等蒽環類聯合化療

5、為代表 20世紀90年代：紫杉醇和多西紫杉醇等紫杉類藥物被稱為腫瘤化療的重大突破江澤飛 紫杉類藥物在乳腺癌化療中的地位和臨床研究進展 中國醫學論壇報網絡版866期當代觀點紫杉類蒽環類聯合化療是治療乳腺癌的最有效方案之一 江澤飛 紫杉類藥物在乳腺癌化療中的地位和臨床研究進展 中國醫學論壇報網絡版866期紫杉醇 vs CMFP目的：比較紫杉醇單藥治療和非蒽環類聯合方案一線化療對轉移性乳腺癌的效果CMFP：環磷酰胺+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試驗設計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腫瘤無進展生存情況估測中位生存期(月)5.36.40.251年腫瘤無進展存活率15%17%2年腫瘤無進展存活率3%5%總生存情況估測中位生存期(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估測生存曲線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結論紫杉醇 vs CMFP生存期更長化療毒性更少生活質量相似控制腫瘤進展相似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）方案對照結果阿霉素+環磷酰胺(AC)CMFP惡心、嘔吐、胃炎發生較高米托蒽醌CMFP對腫瘤控制欠佳紫杉醇CMFP生存期更長，化療毒性更少StocklerThe 2nd International Breast CancerInternational Research Group Conference阿霉素 vs 紫杉醇 vs 聯合方案目的：比較阿霉素、紫杉醇及其聯合方案（AT）一線治療轉移性乳腺癌的效果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 試驗設計每三周重復一次，為一療程。阿霉素(A)紫杉醇(T)聯合方案(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 腫瘤無進展生存時間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周時生存質量（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 結論阿霉素與紫杉醇治療活性相當聯合化療方案在總體有效率和腫瘤無進展時間較好聯合方案與單藥序貫治療的生存期和生活質量相當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提高療效？Gianni：有效率94% CR40%Sparano ：有效率：53% 初治有效率：63% 缺點：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 阿霉素研究對象：接受過含烷化劑化療方案治療的轉移性乳腺癌患者方案多西紫杉醇阿霉素p治療人數161165劑量100mg/m275 g/m2有效率47.8%33.3%0.008腫瘤無進展時間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 有效率優勢比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+長春花堿(MV)目的：比較多西紫杉醇與MV方案對經蒽環類藥物化療的轉移性乳腺癌的療效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有效率優勢比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 多西紫杉醇聯合化療方案 (文獻回顧)有效率：57%-77%中位腫瘤進展時間(TTP)：47-59周2年生存率：60%-67%毒性反應： 以中性粒細胞減少癥及發熱為主 無致死性毒性反應報道 可與阿霉素同時使用而不增加發生充血性心衰 的危險Dr. NabholtzThe 2nd International Breast CancerInternational Res

26、earch Group ConferenceTrastuzumab 抗Her-2/neu人型單克隆抗體 協同作用：鉑劑、多西紫杉醇、放療相加作用：阿霉素、紫杉醇、環磷酰胺目前的研究表明最有效的聯合治療方案為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總體評價22%63%一線治療26%77%二線治療22%61%三線治療15%49%有紫杉醇藥物應用史16%38%無紫杉醇藥物應用史24%