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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,70年代: CMF 80年代: 蒽环类(anthracyclines) 90年代: 紫杉类(taxanes) 21世纪:化疗生物靶向治疗 常规剂量密集,TX方案与AC方案比较,docetaxel/capecitabine (TX) ADM / CTX(AC) 目的:无蒽环类方案与含蒽环类方案比较。 3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,209 例腋窝淋巴结阳性, II/III 期BC行4周期TX or AC . TX与AC
2、比, 增加了 pCR (21% / 10%, P = 0.024) ,RR (84% / 65%, P = 0.003). TX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。 DFS无差别 (P = 0.932). pCR 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 TC,doxorubicin and cyclophosphamide (AC)
3、 docetaxel and cyclophosphamide (TC) 1016 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 TC,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、水肿、粒
4、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 MBC,docetaxel 100 mg/m(2) every 3 weeks RR: 35% MS: 12M MTTP: 4M docetaxel 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. J Cancer
5、 Res Clin Oncol. 2007,Nab-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 new formula
6、tion with an improved safety profile and greater efficacy,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。 nab-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 taxane study.,此
7、为一项前瞻性、多中心、随机对照研究。 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。 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 paclitaxel in metas
8、tatic breast cancer: results of the ERASME 3 study.,MBC患者随机分为AD 组或AP 组,每3周一次。 AD4- docetaxel4 AP4- paclitaxel4,Cassier 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 ERASME 3 study.
9、,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), AD 的血液学毒性比AP 重(p 0.0000)3-4 度疲劳AD重(p = 0.03). 而神经病变在AP组多见 (p = 0.03)。,Cassier PA, et al. Breast Cancer Res Treat. 2007,A phase-III trial of doxorubicin and docetaxel versus d
10、oxorubicin and paclitaxel in metastatic breast cancer: results of the ERASME 3 study.,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.,6个大型临床试验。验证 taxane
11、s 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。 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。,Estvez LG, et al. Cancer Treat Rev. 2007,Combining chemotherapy and low-molecular-weight heparin for the treatment of advanced breast cancer:,凝血激活在肿瘤进展中起作用,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。 Enoxaparin , 0, 5 o
12、r 1.0 mg/kg ,每天一次。 Docetaxel 35-45 mg/m(2),每周一次。 PR: 36%; SD:36,Seeholzer N, et al. Blood Coagul Fibrinolysis. 2007 ;18(5):415-423.,Vinorelbine/docetaxel combination treatment of metastatic breast cancer: a phase I study,方法: DOC: 60 or 70 mg /m2, day 1 NVB: 20 to 25 mg /m2 for i.v. on day 1, 60 mg/
13、m2 on day 8 or day 15 for oral, every 3 weeks.,Bonneterre J, et al. Cancer Chemother Pharmacol. 2007 ; 60(3):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.,gefitinib 250 mg ,once daily doc
14、etaxel 75 mg/m(2) ,every 3 weeks, until tumor progression, toxicity or other reasons for discontinuation.,Dennison SK, et al. Invest New Drugs. 2007,A phase II clinical trial of ZD1839 (Iressatrade mark) in combination with docetaxel as first-line treatment in patients with advanced breast cancer.,3
15、3例,中位治疗周期为5周期。临床受益率为51.5%。 CR: 1; PR: 12; SD: 4; ORR: 39.4%。,Dennison SK, et al. Invest New Drugs. 2007,A phase II clinical trial of ZD1839 (Iressatrade mark) in combination with docetaxel as first-line treatment in patients with advanced breast cancer.,CONCLUSION: The combination of gefitinib and d
16、ocetaxel is an active regimen in patients with previously untreated MBC.,Dennison SK, et al. Invest New Drugs. 2007,Multicenter phase II trial of neoadjuvant therapy with trastuzumab, docetaxel, and carboplatin for human epidermal growth factor receptor-2-overexpressing stage II or III breast cancer: results of the GETN(A)-1 trial.,方法: HER-2-阳性患者。 trastuzumab 4 mg/kg (day 1), followed by 2 mg/kg weekly, docetaxel 75 mg/m2, every 3 weeks, carboplatin (area under curve