乳腺癌化疗进展-PPT精选课件

1、乳腺癌化疗进展紫杉醇药物在乳腺癌中的应用乳腺癌流行病学 发病率在逐年上升 张忠清 乳腺癌当前流行趋势分析 中国肿瘤 2000 9（10）：454 年份 全球 我国新发例数（万）发病率（1/10万）新发例数（万）发病率（1/10万）197554.123.75.412.3198057.225.83.16.4198571.929.86.713.1199079.530.36.111.0乳腺癌流行病学 死亡率国家死亡率（1/10万）国家死亡率（1/10万）国家死亡率（1/10万）丹麦26.4意大利20.7希腊15.9荷兰25.3澳大利亚20.2保加利亚14.8英国25.1法国19.7秘鲁14.2瑞士22

2、.6西班牙17.4哈萨克斯坦12.8德国22.1葡萄牙17.4哥伦比亚9.1奥地利21.8瑞典17.3墨西哥8.9捷克21.6波兰16.3日本7.1阿根廷21.2俄罗斯16.3中国城区6.2加拿大20.9罗马尼亚16.0美国20.7匈牙利15.9张忠清 乳腺癌当前流行趋势分析 中国肿瘤 2000 9（10）：454死亡率下降的原因生活方式改变早期诊断率提高治疗方法改进张忠清 乳腺癌当前流行趋势分析 中国肿瘤 2000 9（10）：454乳腺癌在常见肿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张

3、忠清 乳腺癌当前流行趋势分析 中国肿瘤 2000 9（10）：454预后和预测因素肿瘤大小分化程度组织侵犯情况淋巴结转移情况（淋巴）结外转移情况肿瘤倍增速率ERPgRErb B-2EGRF Dr. Ann ThorThe 2nd International Breast Cancer International Research Group Conference ER和PgR对肿瘤复发有预示作用ER(+)与()：5年内生存率差别较为显著 5-10年以后两者差别不大 Dr. Ann ThorThe 2nd International Breast Cancer International Res

4、earch Group Conference erbB-2对侵袭性导管癌的复发有预示作用erbB-2（+）高剂量化疗 敏感 （-）高剂量化疗 不敏感erbB-2（+）对含蒽环霉素的化疗方案疗效更好erbB-2（+）对CMF方案的受益有限erbB-2（+）+EGRF（+）预后不良 Dr. Ann ThorThe 2nd International Breast Cancer International Research Group Conference 乳腺癌化疗进展乳腺癌化疗回顾20世纪70年代：环磷酰胺、甲氨蝶呤、氟脲嘧啶等非蒽环类药物为主 20世纪80年代：阿霉素、表阿霉素等蒽环类联合化疗

5、为代表 20世纪90年代：紫杉醇和多西紫杉醇等紫杉类药物被称为肿瘤化疗的重大突破江泽飞 紫杉类药物在乳腺癌化疗中的地位和临床研究进展 中国医学论坛报网络版866期当代观点紫杉类蒽环类联合化疗是治疗乳腺癌的最有效方案之一 江泽飞 紫杉类药物在乳腺癌化疗中的地位和临床研究进展 中国医学论坛报网络版866期紫杉醇 vs CMFP目的：比较紫杉醇单药治疗和非蒽环类联合方案一线化疗对转移性乳腺癌的效果CMFP：环磷酰胺+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试验设计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结果紫

7、杉醇（n=107）CMFP（n=102）P值有效率完全+部分29%35%0.37肿瘤无进展生存情况估测中位生存期(月)5.36.40.251年肿瘤无进展存活率15%17%2年肿瘤无进展存活率3%5%总生存情况估测中位生存期(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估测生存曲线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生活质量改变情况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结论紫杉醇 vs CMFP生存期更长化疗毒性更少生活质量相似控制肿瘤进展相似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紫杉醇单药治疗乳腺癌与其它常用化疗方案比较（荟萃分析）方案对照结果阿霉素+环磷酰胺(AC)CMFP恶心、呕吐、胃炎发生较高米托蒽醌CMFP对肿瘤控制欠佳紫杉醇CMFP生存期更长，化疗毒性更少StocklerThe 2nd International Breast CancerInternational Research Group Conference阿霉素 vs 紫杉醇 vs 联合方案目的：比较阿霉素、紫杉醇及其联合方案（AT）一线治疗转移性乳腺癌的效果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 试验设计每三周重复一次，为一疗程。阿霉素(A)紫杉醇(T)联合方案(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 治疗有效率（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 肿瘤无进展生存时间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周时生存质量（QOL）比较P=NS分组A(n=136)T(n=150)A+T(n=165)治疗前QOL107.5110.3111.016周时QOL105.8107.4108.0QOL改变-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 结论阿霉素与紫杉醇治疗活性相当联合化疗方案在总体有效率和肿瘤无进展时间较好联合方案与单药序贯治疗的生存期和生活质量相当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+紫杉醇增加用药剂量是否会提高疗效？Gianni：有效率94% CR40%Sparano ：有效率：53% 初治有效率：63% 缺点：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、发生较少Dr. George SledgeThe 2nd International Breast CancerInternational Research Group Conference多西紫杉醇 vs 阿霉素研究对象：接受过含烷化剂化疗方案治疗的转移性乳腺癌患者方案多西紫杉醇阿霉素p治疗人数161165剂量100mg/m275 g/m2有效率47.8%33.3%0.008肿瘤无进展时间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 有效率优势比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治疗有效率

20、曲线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丝裂霉素+长春花碱(MV)目的：比较多西紫杉醇与MV方案对经蒽环类药物化疗的转移性乳腺癌的疗效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 化疗方案多西紫杉醇MV治疗人数203189剂量100 mg/m2 (3周一次)M:12 mg/m2 (6周一次)V:6 mg/m2 (3周一次)最大疗程：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有效率优势比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生存率曲线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 多西紫杉醇联合化疗方案 (文献回顾)有效率：57%-77%中位肿瘤进展时间(TTP)：47-59周2年生存率：60%-67%毒性反应： 以中性粒细胞减少症及发热为主 无致死性毒性反应报道 可与阿霉素同时使用而不增加发生充血性心衰 的危险Dr. NabholtzThe 2nd International Breast CancerInternational Res

26、earch Group ConferenceTrastuzumab 抗Her-2/neu人型单克隆抗体 协同作用：铂剂、多西紫杉醇、放疗相加作用：阿霉素、紫杉醇、环磷酰胺目前的研究表明最有效的联合治疗方案为Weekly Paclitalx /carboplatin with Herceptin.Dr. NabholtzThe 2nd International Breast CancerInternational Research Group Conference紫杉醇周剂量化疗方案紫杉醇CR+PRCR+PR+ST总体评价22%63%一线治疗26%77%二线治疗22%61%三线治疗15%49%有紫杉醇药物应用史16%38%无紫杉醇药物应用史24%