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1、乳腺癌的化疗进展桂林医学院附属医院肿瘤一科康马飞乳腺癌化疗的历史回顾l70年代： CMFl80年代： 蒽环类（anthracyclines）l90年代： 紫杉类（taxanes)l21世纪：化疗生物靶向治疗l常规剂量密集TX方案与AC方案比较ldocetaxel/capecitabine (TX)lADM / CTX(AC) l目的：无蒽环类方案与含蒽环类方案比较。l3期单中心随机试验。 Lee KS, et al. Breast Cancer Res Treat. 2007 TX方案与AC方案比较l209 例腋窝淋巴结阳性， II/III 期BC行4周期TX or AC . lTX与AC比,
2、 增加了 pCR (21% / 10%, P = 0.024) ，RR (84% / 65%, P = 0.003). lTX恶心、呕吐少，但口腔炎、腹泻, 肌肉痛，皮 肤及指甲改变比AC明显。 lDFS无差别 (P = 0.932). lpCR 者复发少(P = 0.025; hazard ratio, 0.189; 95% CI, 0.044-0.815). Lee KS, et al. Breast Cancer Res Treat. 2007 Phase III trial comparing AC with TCldoxorubicin and cyclophosphamide (A
3、C) ldocetaxel and cyclophosphamide (TC) l1016 例 AC (n = 510) TC (n = 506), every 3 weeks. 完成化疗后给予放疗，受体阳性者给予 tamoxifen, Jones SE, et al. J Clin Oncol. 2006 ; 24(34): 5381-5387. Phase III trial comparing AC with TCl结果: TC的 5年 DFS 明显高于AC (86% v 80%, P =0 .015). ORR: TC / AC 90% / 87%, P =0 .13. 肌肉痛、关节痛
4、、水肿、粒细胞减少在TC 组多见。 恶心、呕吐，充血性心衰在AC组多见。 Jones SE, et al. J Clin Oncol. 2006 ; 24(34): 5381-5387. A phase II trial of docetaxel as second-line chemotherapy in patients with MBCl docetaxel 100 mg/m(2) every 3 weeks lRR: 35%lMS: 12MlMTTP: 4Mldocetaxel 是治疗MBC的有效2线药物，特 别是对 anthracycline耐药的病人。 Baur M, et al.
5、 J Cancer Res Clin Oncol. 2007 lNab-paclitaxel (ABI-007, Abraxane) 是将paclitaxel包裹在白蛋白里。Henderson IC, et al. Expert Rev Anticancer Ther. 2007 ; 7(7):919-943. Nab-paclitaxel for breast cancer: a new formulation with an improved safety profile and greater efficacy Nab-paclitaxel for breast cancer: a ne
6、w formulation with an improved safety profile and greater efficacy l随机 II 期临床试验提示 每周一次nab- paclitaxel 比每3周一次nab-paclitaxel或 docetaxel更有效、更安全。lnab-paclitaxel 的优势在于安全性提高，可 以增加剂量，且进入肿瘤细胞内的药物比 例更高。Henderson IC, et al. Expert Rev Anticancer Ther. 2007 ; 7(7):919-943. The trastuzumab and vinorelbine or ta
7、xane study. l此为一项前瞻性、多中心、随机对照研究。 l方法: HER2过度表达的 MBC ，未进行过化疗的 病人随机分为trastuzumab vinorelbine 每周一次。trastuzumab taxane 每周一次。 l结论: vinorelbine/trastuzumab 和 taxane/trastuzumab 一线治疗HER2阳性的 MBC 疗效无差异。Burstein HJ, et al. Cancer. 2007 A phase-III trial of doxorubicin and docetaxel versus doxorubicin and pacl
8、itaxel in metastatic breast cancer: results of the ERASME 3 study.lMBC患者随机分为AD 组或AP 组，每3周 一次。AD4- docetaxel4 AP4- paclitaxel4Cassier PA, et al. Breast Cancer Res Treat. 2007 A phase-III trial of doxorubicin and docetaxel versus doxorubicin and paclitaxel in metastatic breast cancer: results of the E
9、RASME 3 study.l结果: RR: 39.6% for AD and 41.8% for AP. median PFS 和 median OS： 8.7 M和 21.4 M( AD) ； 8.0M 和 27.3 M(AP) (p = 0.977 and 0.081), lAD 的血液学毒性比AP 重(p 0.0000）3-4 度疲劳AD重(p = 0.03). l而神经病变在AP组多见 (p = 0.03)。Cassier PA, et al. Breast Cancer Res Treat. 2007A phase-III trial of doxorubicin and doce
10、taxel versus doxorubicin and paclitaxel in metastatic breast cancer: results of the ERASME 3 study.l结论：AD与AP在生活质量和有效率无差别，但在副作用方面有差别。Cassier PA, et al. Breast Cancer Res Treat. 2007 Evidence-based use of taxanes in the adjuvant setting of breast cancer. A review of randomized phase III trials.l6个大型临床
11、试验。验证 taxanes 在乳腺癌辅助治疗中的作用。各种不同的以 anthracycline为主的方案作为对照组。l有充分证据支持常规使用taxanes 治疗乳腺 癌是有益的，包括激素受体阳性和Her-2阳性的病人。EstvezEstvez LG LG, et al. , et al. Cancer Treat Rev.Cancer Treat Rev. 2007 2007 Combining chemotherapy and low-molecular-weight heparin for the treatment of advanced breast cancer: l凝血激活在肿瘤进
12、展中起作用，低分子肝素可影 响肿瘤生长，显示低分子肝素可影响化疗疗效。lEnoxaparin , 0, 5 or 1.0 mg/kg ，每天一次。 Docetaxel 35-45 mg/m(2)，每周一次。 lPR: 36%; SD:36SeeholzerSeeholzer N N, et al. , et al. Blood Blood CoagulCoagul FibrinolysisFibrinolysis. . 2007 ;18(5):415-423. 2007 ;18(5):415-423.Vinorelbine/docetaxel combination treatment of
13、metastatic breast cancer: a phase I study l方法: DOC: 60 or 70 mg /m2, day 1 NVB: 20 to 25 mg /m2 for i.v. on day 1, 60 mg/ m2 on day 8 or day 15 for oral,every 3 weeks. BonneterreBonneterre J J, et al. , et al. Cancer Cancer ChemotherChemother PharmacolPharmacol. . 2007 ; 60(3):365-373. 2007 ; 60(3):
14、365-373.A phase II clinical trial of ZD1839 (Iressatrade mark) in combination with docetaxel as first-line treatment in patients with advanced breast cancer.lgefitinib 250 mg ，once daily docetaxel 75 mg/m(2) ，every 3 weeks, until tumor progression, toxicity or other reasons for discontinuation. Denn
15、ison SK, et al. Invest New Drugs. 2007Dennison SK, et al. Invest New Drugs. 2007A phase II clinical trial of ZD1839 (Iressatrade mark) in combination with docetaxel as first-line treatment in patients with advanced breast cancer.l33例，中位治疗周期为5周期。临床受益率为51.5%。lCR: 1; PR: 12; SD: 4; ORR: 39.4%。Dennison
16、SK, et al. Invest New Drugs. 2007Dennison SK, et al. Invest New Drugs. 2007A phase II clinical trial of ZD1839 (Iressatrade mark) in combination with docetaxel as first-line treatment in patients with advanced breast cancer.lCONCLUSION:The combination of gefitinib and docetaxel is an active regimen in patients with previously untreated MBC. Dennison SK, et al. Invest New Drugs. 2007Dennison SK, et al. Invest New Drugs. 2007Mult
