乳腺癌的化疗进展课件.ppt

《乳腺癌的化疗进展课件.ppt》由会员分享，可在线阅读，更多相关《乳腺癌的化疗进展课件.ppt（70页珍藏版）》请在三一办公上搜索。

1、乳腺癌化疗的历史回顾,70年代： CMF80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,乳腺癌化疗的历史回顾70年代： CMF,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docetaxel/capecitab,TX方案与AC方案比较,209 例腋窝淋巴结阳性， II/III 期BC行4

2、周期TX or AC .TX与AC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,TX方案与AC方案比较209 例腋窝淋巴结阳性， II/II,Phase III trial comparing A

3、C with TC,doxorubicin and cyclophosphamide (AC) 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 w,Phase III trial comparing AC with TC,结果: TC的 5年 DFS

4、 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.,Phase III trial comparing AC w,A phase II trial of docetaxel as second-line chemotherapy in patients with MBC,docetaxel 100 mg/m(2) ev

5、ery 3 weeks RR: 35%MS: 12MMTTP: 4Mdocetaxel 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 Res Clin Oncol. 2007,A phase II trial of docetaxel,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 f

6、or breast cancer: a new formulation with an improved safety profile and greater efficacy,Henderson IC, et al. Expert Re,Nab-paclitaxel for breast cancer: a new formulation 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-

7、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.,Nab-paclitaxel for breast canc,The trastuzumab and vinorelbine or taxane study.,此为一项前瞻性、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

8、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,The trastuzumab and vinorelbin,A phase-III trial of doxorubicin and docetaxel versus doxorubicin and paclitaxel in metastatic breast cancer: results of the ERASME 3 study.,MBC患者随机分为AD 组或AP 组，每3周

9、一次。 AD4- docetaxel4 AP4- paclitaxel4,Cassier PA, et al. Breast Cancer Res Treat. 2007,A phase-III trial of doxorubic,A phase-III trial of doxorubicin and docetaxel versus doxorubicin and paclitaxel in metastatic breast cancer: results of the ERASME 3 study.,结果: RR: 39.6% for AD and 41.8% for AP. med

10、ian 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 doxorubic,A phase-III trial of doxorubicin and docetaxel versus doxorubicin a

11、nd 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,A phase-III trial of doxorubic,Evidence-based use of taxanes in the adjuvant setting of breast cancer. A review of randomized phase III trials.

12、,6个大型临床试验。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。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,Evidence-based use of taxanes,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，

13、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 or 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.,Combining chemotherapy and low,Vinorelbine/docetaxel combination treatment of metastatic breast cancer: a phase I study,方

14、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.,Bonneterre J, et al. Cancer Chemother Pharmacol. 2007 ; 60(3):365-373.,Vinorelbine/docetaxel combinat,A phase II clinical trial of ZD1839 (Iressatrade mark) in combination wit

15、h docetaxel as first-line treatment in patients with advanced breast cancer.,gefitinib 250 mg ，once daily docetaxel 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 Z,A phase II

16、clinical trial of ZD1839 (Iressatrade mark) in combination with docetaxel as first-line treatment in patients with advanced breast cancer.,33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 Z,A phase II clinical trial

17、of ZD1839 (Iressatrade mark) in combination with docetaxel as first-line treatment in patients with advanced breast cancer.,CONCLUSION: The combination of gefitinib and docetaxel is an active regimen in patients with previously untreated MBC.,Dennison SK, et al. Invest New Drugs. 2007,A phase II cli

18、nical trial of Z,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

19、weekly, docetaxel 75 mg/m2， every 3 weeks, carboplatin (area under curve, 6) for six cycles,Coudert BP, et al. J Clin Oncol. 2007; 25(19):2678-2684.,Multicenter phase II trial of,Multicenter phase II trial of neoadjuvant therapy with trastuzumab, docetaxel, and carboplatin for human epidermal growth

20、 factor receptor-2-overexpressing stage II or III breast cancer: results of the GETN(A)-1 trial.,RESULTS: Sixty-seven patients, HER-2-positive, completed six cycles of therapy. CR and PR: 95% (85% and 10%). Grade 3/4 neutropenia and febrile neutropenia were 2%. No symptomatic cardiac dysfunction occ

21、urred.,Coudert BP, et al. J Clin Oncol. 2007; 25(19):2678-2684.,Multicenter phase II trial of,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(

22、A)-1 trial.,CONCLUSION: Trastuzumab plus docetaxel and carboplatin achieved a good pCR rate and favorable tolerability in stage II or III HER-2-positive breast cancer.,Coudert BP, et al. J Clin Oncol. 2007; 25(19):2678-2684.,Multicenter phase II trial of,Pathologic complete response with six compare

23、d with three cycles of neoadjuvant epirubicin plus docetaxel and granulocyte colony-stimulating factor in operable breast cancer: results of ABCSG-14.,epirubicin 75 mg/m2 docetaxel 75 mg/m2 on day 1 granulocyte colony-stimulating factor on days 3 through 10 , ED+G every 21 days, three or six cycles.

24、,Steger GG, et al. J Clin Oncol. 2007; 25(15):2012-2018.,Pathologic complete response w,Pathologic complete response with six compared with three cycles of neoadjuvant epirubicin plus docetaxel and granulocyte colony-stimulating factor in operable breast cancer: results of ABCSG-14.,Six cycles of ED

25、+G, compared with three cycles, resulted in a significantly higher pCR rate (18.6% v 7.7%, P = .0045), a higher percentage of patients with negative axillary status (56.6% v 42.8%, P = .02). Rates of adverse events were similar, and no patients died on treatment.,Steger GG, et al. J Clin Oncol. 2007

26、; 25(15):2012-2018.,Pathologic complete response w,Phase II study of neoadjuvant docetaxel/ vinorelbine followed by surgery and adjuvant doxorubicin/cyclophosphamide in women with stage II/III breast cancer.,before surgery with 6 cycles of docetaxel 60 mg/m2 and vinorelbine 45 mg/m2, repeated every

27、2 weeks with granulocyte colony-stimulating factor and quinolone prophylaxis.,Limentani SA, et al. Clin Breast Cancer. 2006;6(6):511-517. .,Phase II study of neoadjuvant,Phase II study of neoadjuvant docetaxel/ vinorelbine followed by surgery and adjuvant doxorubicin/cyclophosphamide in women with s

28、tage II/III breast cancer.,RESULTS: 59 patients, RR: 98%, CR:63%. Grade 3/4 neutropenia (95%), neutropenic fever (22%), mucositis (5%), and pulmonary toxicity (5%).,Limentani SA, et al. Clin Breast Cancer. 2006;6(6):511-517. .,Phase II study of neoadjuvant,Dosage of capecitabine and cyclophosphamide

29、 combination therapy in patients with metastatic breast cancer,oral capecitabine 628 to 829 mg/m2 twice daily (bid) oral cyclophosphamide 33 to 50 mg/m2 bid, on days 1 to 14 a cycle every 21 days.,Ohno S, et al. Anticancer Res. 2007;27(2):1009-1013.,Dosage of capecitabine and cyc,Dosage of capecitab

30、ine and cyclophosphamide combination therapy in patients with metastatic breast cancer,CONCLUSION: The capecitabine/cyclophosphamide combination regimen is well tolerated and active in MBC, and is being evaluated in a phase II study in anthracycline-pretreated MBC.,Ohno S, et al. Anticancer Res. 200

31、7;27(2):1009-1013.,Dosage of capecitabine and cyc,Phase I/II trial of adjuvant dose-dense docetaxel/epirubicin/cyclophosphamide (TEC) in stage II and III breast cancer.,docetaxel (T) 75 mg/m(2), epirubicin (E) 75 mg/m(2) (cohort 1, n = 3) or 100 mg/m(2) (cohort 2, n = 12), cyclophosphamide (C) 500 m

32、g/m(2) day 1, with pegfilgrastim 6 mg subcutaneously on day 2, every 2 weeks for six cycles.,Burdette-Radoux S, et al. Breast J. 2007;13(3):274-280.,Phase I/II trial of adjuvant d,Phase I/II trial of adjuvant dose-dense docetaxel/epirubicin/cyclophosphamide (TEC) in stage II and III breast cancer.,结

33、论: 剂量密度 TEC 化疗是可行的。与TAC等剂量时 (docetaxel 75 mg/m(2), epirubicin 75 mg/m(2), cyclophosphamide 600 mg/m(2), 毒性反应中等。,Burdette-Radoux S, et al. Breast J. 2007;13(3):274-280.,Phase I/II trial of adjuvant d,Gemcitabine Plus Doxorubicin as First-Line Treatment in Advanced or Metastatic Breast Cancer (MBC), A

34、 Phase II Study.,gemcitabine 1250mg/m2 IV on days 1 , 8 doxorubicin 60mg/m2 IV on day 1 every 21 days, for 6 cycles.,El Serafi MM, et al. J Egypt Natl Canc Inst. 2006;18(3):209-215.,Gemcitabine Plus Doxorubicin a,Gemcitabine Plus Doxorubicin as First-Line Treatment in Advanced or Metastatic Breast C

35、ancer (MBC), A Phase II Study.,RESULTS: CR:17.1% PR40% SD: 22.9% ORR: 57.1%. MTTP: 7 months The overall survival at 1 and 2 years was 74.2% and 34.2%;,El Serafi MM, et al. J Egypt Natl Canc Inst. 2006;18(3):209-215.,Gemcitabine Plus Doxorubicin a,Gemcitabine in the management of metastatic breast ca

36、ncer: a systematic review.,共83个试验，包括4个III 期随机临床试验，全部III 期临床试验均为一线用药。结果：其中2个III期试验证明含gemcitabine方案治疗MBC疗效高，副作用小。而另外2个III期试验却 认为没有临床受益，而副作用大。结论: Gemcitabine taxane一线或二线治疗MBC疗效显著。,Dent S, et al. Breast Cancer Res Treat. 2007,Gemcitabine in the management,Low dose Gemcitabine plus cisplatin in a weekly-

37、based regimen as salvage therapy for relapsed breast cancer after taxane-anthracycline-containing regimens.,gemcitabine (G) (initial dose 750 mg/m(2), or 600 mg/m(2) if the patient had received more than two previous CT lines) plus cisplatin (P) (initial dose 30 mg/m(2), or 20 mg/m(2) in case of /=3

38、 prior CT lines) on days 1 and 8 of a 21-day cycle. Treatment was postponed to day 15 if it could not be given on day 8, without dose reduction. If treatment could not be given on day 15, a 20% dose reduction was allowed and treatment given the next week.,Snchez-Escribano Morcuende R, et al. Clin Tr

39、ansl Oncol. 2007; 9(7):459-464.,Low dose Gemcitabine plus cisp,Low dose Gemcitabine plus cisplatin in a weekly-based regimen as salvage therapy for relapsed breast cancer after taxane-anthracycline-containing regimens.,All had prior anthracyclines and taxanes. Other agents used included 5-FU/enilura

40、cil, MTX, RPR 109881A, trastuzumab, cisplatin, VP16, vinorelbine, capecitabine and irinotecan. 72.7% had received radiotherapy 68.1% hormonal therapy.,Snchez-Escribano Morcuende R, et al. Clin Transl Oncol. 2007; 9(7):459-464.,Low dose Gemcitabine plus cisp,Low dose Gemcitabine plus cisplatin in a w

41、eekly-based regimen as salvage therapy for relapsed breast cancer after taxane-anthracycline-containing regimens.,Results: PR: 9.1%, SD: 36.4%. Clinical Benefit Rate (PR+SD): 45.5% MTTP: 4 months Median survival: 8 months Toxicities grade 3 were neutropenia 35% and thrombocytopenia 15%.,Snchez-Escri

42、bano Morcuende R, et al. Clin Transl Oncol. 2007; 9(7):459-464.,Low dose Gemcitabine plus cisp,Low dose Gemcitabine plus cisplatin in a weekly-based regimen as salvage therapy for relapsed breast cancer after taxane-anthracycline-containing regimens.,结论: 曾进行过多次化疗的， PS较好的MBC. 每周一次的 cisplatin-gemcitab

43、ine 是安全有效的挽救治疗方案。,Snchez-Escribano Morcuende R, et al. Clin Transl Oncol. 2007; 9(7):459-464.,Low dose Gemcitabine plus cisp,Dose-finding study of capecitabine in combination with weekly paclitaxel for patients with anthracycline-pretreated metastatic breast cancer.,CONCLUSION: capecitabine 1,000 mg

44、/m(2) twice daily, days 1-14, paclitaxel 60 mg/m(2)/week. paclitaxel 剂量大于60 mg/m(2)/week 是不合适的，因出现严重的皮肤毒性。,Susnjar S, et al. J BUON. 2007;12(2):189-196.,Dose-finding study of capecita,A phase II study of trastuzumab and capecitabine for patients with HER2-overexpressing metastatic breast cancer: Jap

45、an Breast Cancer Research Network (JBCRN) 00 Trial.,59 例病人由6 个中心提供。进行 trastuzumab capecitabine治疗乳腺癌的研究。86接受过化疗 。 CMF (7.1%), anthracyclines (28.6%), taxanes (25.0%), 或两种方案化疗(25.0%)。,Yamamoto D, et al. Cancer Chemother Pharmacol. 2007 .,A phase II study of trastuzuma,A phase II study of trastuzumab a

46、nd capecitabine for patients with HER2-overexpressing metastatic breast cancer: Japan Breast Cancer Research Network (JBCRN) 00 Trial.,RR：65.0% (trastuzumab + capecitabine 作为MBC的一线治疗 ) ，有效者62.5% 在HER2 +3的患者中, 二线或三线治疗者也有许多有效。trastuzumab capecitabine 作为一线治疗比作为二、三线治疗有更长的 TTP 和OS。,Yamamoto D, et al. Can

47、cer Chemother Pharmacol. 2007 .,A phase II study of trastuzuma,Phase II study of capecitabine plus trastuzumab in human epidermal growth factor receptor 2 overexpressing metastatic breast cancer pretreated with anthracyclines or taxanes.,27例HER-2-过度表达的MBC，曾用 anthracyclines and/or taxanes 治疗，给予口服cape

48、citabine 1,250 mg/m(2)， bid， 114 天。 trastuzumab 4 mg/kg ，第1天，以后每周 2 mg/kg。RR: 45%, CR: 15%, PR:30%. SD: 33%. MOS: 28 M. MPFS: 6.7 M.,Schaller G, et al. J Clin Oncol. 2007;25(22):3246-50.,Phase II study of capecitabine,Vinorelbine and cisplatin for metastatic breast cancer: a salvage regimen in patie

49、nts progressing after docetaxel and anthracycline treatment.,Cisplatin : 75 mg/m2 on day 1 VNR: 25 mg/m2 on days 1 , 8 every 3 weeks.CR: 5.6% ; PR: 41.6%; OR: 47.2% neutropenia grade : 47%. Thrombocytopenia grade 3/4 :11%. There were no treatment-related deaths.,Vassilomanolakis M, et al. Cancer Inv

50、est. 2003;21(4):497-504.,Vinorelbine and cisplatin for,Vinorelbine and cisplatin for metastatic breast cancer: a salvage regimen in patients progressing after docetaxel and anthracycline treatment.,结论: DDP / VNR 耐受好，且对anthracyclines 和docetaxel 耐药的病人有效。.,Vassilomanolakis M, et al. Cancer Invest. 2003