乳腺癌化疗进展

null乳腺癌化疗进展乳腺癌化疗进展——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 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 Erb B-2 EGRF Dr. Ann Thor The 2nd International Breast Cancer International Research Group Conference ER和PgRER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-2erbB-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 乳腺癌化疗进展乳腺癌化疗进展乳腺癌化疗回顾乳腺癌化疗回顾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 Clin Oncol. 1999 Aug;17(8):2355试验设计试验设计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结果结果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估测生存曲线估测生存曲线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):2355生活质量改变情况生活质量改变情况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结论结论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）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,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 试验设计试验设计 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 paclitaxel 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）治疗有效率（CR+PR）A vs T P =0.84 A vs AT P =0.07 T vs AT P=0.04Sledge 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 肿瘤无进展生存时间肿瘤无进展生存时间A vs T p=0.68 A vs AT p=0.03 T vs AT p=0.09Sledge 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 中位生存期中位生存期 P=NSSledge GW. Phase III trial of doxorubicin,paclitaxel,and the combination of doxorubicin and paclitaxel as front-line chemotherapy for metastatic breast cancer: an intergroup trial (E1193). J Clin Oncol. 2003 Feb 15;21(4):588 16周时生存质量（QOL）比较16周时生存质量（QOL）比较 P=NSSledge 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-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 Sledge The 2nd International Breast CancerInternational Research Group Conference表阿霉素+紫杉醇表阿霉素+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. 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 阿霉素 ——有效率优势比多西紫杉醇 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. 1999 Aug;17(8):2341 多西紫杉醇 vs 阿霉素 ——Kaplan-Meier治疗有效率曲线多西紫杉醇 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)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 vinblastine in patients with metastatic breast cancer progressing despite previous anthracycline-containing chemotherapy. 304 Study Group. J Clin Oncol. 1999 May;17(5):1413-24 化疗方案化疗方案Nabholtz JM. Prospective randomized trial of docetaxel versus mitomycin plus vinblastine in patients with metastatic breast cancer progressing despite previous anthracycline-containing chemotherapy. 304 Study Group. J Clin Oncol. 1999 May;17(5):1413-24 有效率有效率Nabholtz JM. Prospective randomized trial of docetaxel versus mitomycin plus vinblastine in 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 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 ——Kaplan-Meier生存率曲线多西紫杉醇 vs MV ——Kaplan-Meier生存率曲线Nabholtz JM. Prospective randomized trial of docetaxel versus mitomycin plus vinblastine in patients with metastatic breast cancer progressing despite previous anthracycline-containing chemotherapy. 304 Study Group. J Clin Oncol. 1999 May;17(5):1413-24 多西紫杉醇联合化疗方案 (文献回顾)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 Research Group ConferenceTrastuzumab 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紫杉醇周剂量化疗方案Dr. Burris The 2nd International Breast CancerInternational Research Group ConferencenullA, 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！ 谢 谢！