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,乳腺癌流行病学 死亡率,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,张忠清 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,ER PgR E
2、rb B-2 EGRF,Dr. Ann Thor The 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 Thor The 2nd International Breast Cancer International Research 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
3、-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 Thor The 2nd International Breast Cancer International Research Group Conference,乳腺癌化疗进展,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
4、,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 chemotherapy as front-line therapy in untreated metastatic breast cancer. J
5、 Clin Oncol. 1999 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. 1999 Aug;17(8):2355,结果,Bishop JF. Initial paclitaxel improves outcome compared with CMFP combina
6、tion chemotherapy as front-line therapy in untreated metastatic breast cancer. J Clin Oncol. 1999 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. 1999 Aug;17(8)
7、:2355,生活质量改变情况,Bishop JF. Initial paclitaxel improves outcome compared with CMFP combination chemotherapy as front-line therapy in untreated metastatic breast cancer. J Clin Oncol. 1999 Aug;17(8):2355,结论,Bishop JF. Initial paclitaxel improves outcome compared with CMFP combination chemotherapy as fr
8、ont-line therapy in untreated metastatic breast cancer. J Clin Oncol. 1999 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）,Stockler The 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 doxorubicin,p
9、aclitaxel,and the combination of doxorubicin and paclitaxel as front-line chemotherapy for metastatic breast cancer: an intergroup trial (E1193). J Clin Oncol. 2003 Feb 15;21(4):588,试验设计,每三周重复一次，为一疗程。,Sledge GW. Phase III trial of doxorubicin,paclitaxel,and the combination of doxorubicin and paclita
10、xel as front-line chemotherapy for metastatic breast cancer: an intergroup trial (E1193). J Clin Oncol. 2003 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=0.04,Sledge GW. Phase III trial of doxorubicin,paclitaxel,and the combination of doxorubicin and paclitaxel as front-line
11、chemotherapy for metastatic breast cancer: an intergroup trial (E1193). J Clin Oncol. 2003 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=0.09,Sledge GW. Phase III trial of doxorubicin,paclitaxel,and the combination of doxorubicin and paclitaxel as front-line chemotherapy for metast
12、atic breast cancer: an intergroup trial (E1193). J Clin Oncol. 2003 Feb 15;21(4):588,中位生存期,P=NS,Sledge GW. Phase III 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. 2
13、003 Feb 15;21(4):588,16周时生存质量（QOL）比较,P=NS,Sledge GW. Phase III 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. 2003 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
14、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-line chemotherapy for metastatic breast cancer: an intergroup trial (E1193). J Clin Oncol. 2003 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% Spa
15、rano ：有效率：53%初治有效率：63%缺点：充血性心衰,Dr. George Sledge The 2nd International Breast CancerInternational Research Group Conference,表阿霉素+紫杉醇,有效率40%-80%充血性心衰发生较少,Dr. George Sledge The 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,Chan S. Prosp
16、ective randomized trial of docetaxel versus doxorubicin in patients with metastatic breast cancer. The 303 Study Group. J Clin Oncol. 1999 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
17、Group. J Clin Oncol. 1999 Aug;17(8):2341,多西紫杉醇 vs 阿霉素 Kaplan-Meier治疗有效率曲线,Chan S. Prospective randomized trial of docetaxel versus doxorubicin in patients with metastatic breast cancer. The 303 Study Group. J Clin Oncol. 1999 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,Na
18、bholtz JM. Prospective randomized trial of docetaxel versus mitomycin plusvinblastine in patients with metastatic breast cancer progressing despite previous anthracycline-containing chemotherapy. 304 Study Group.J Clin Oncol. 1999 May;17(5):1413-24,化疗方案,Nabholtz JM. Prospective randomized trial of d
19、ocetaxel versus mitomycin plusvinblastine in patients with metastatic breast cancer progressing despite previous anthracycline-containing chemotherapy. 304 Study Group.J Clin Oncol. 1999 May;17(5):1413-24,有效率,Nabholtz JM. Prospective randomized trial of docetaxel versus mitomycin plusvinblastine in
20、patients with metastatic breast cancer progressing despite previous anthracycline-containing chemotherapy. 304 Study Group.J Clin Oncol. 1999 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 plusvinblastine in patients with metastatic breas
21、t cancer progressing despite previous anthracycline-containing chemotherapy. 304 Study Group.J Clin Oncol. 1999 May;17(5):1413-24,多西紫杉醇 vs MV Kaplan-Meier生存率曲线,Nabholtz JM. Prospective randomized trial of docetaxel versus mitomycin plusvinblastine in patients with metastatic breast cancer progressin
22、g despite previous anthracycline-containing chemotherapy. 304 Study Group.J Clin Oncol. 1999 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. Nabholtz The 2nd International Breast CancerInternational Researc
23、h Group Conference,Trastuzumab,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. Nabholtz The 2nd International Breast CancerInternational Research Group Conference,紫杉醇周剂量化疗方案,Dr. Burris The 2nd International Breast CancerInterna
24、tional Research Group Conference,A, doxorubicin; C, cyclophosphamide; D, docetaxel; F, 5-fluorouracil; P, paclitaxel; DFS, disease-free survival; NS, not significant. P values based upon Cox model.,紫杉醇类在乳腺癌辅助治疗中的地位,总结,目前紫杉类化疗药物是乳腺癌辅助治疗和晚期乳腺癌解救治疗最有效的药物之一。 单药和联合用药均显示很好的疗效。 缩短化疗间隙的密集化疗能进一步提高疗效。,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,谢 谢！,
