原发性肝癌的化疗

null原发性肝癌的化疗 原发性肝癌的化疗 谢伟敏 博士 副教授 胡晓桦 教授 广西医科大学附属肿瘤医院 化疗一科null背 景近二十年来，全世界范围内不管是发达国家（如美国）还是发展中国家或贫穷落后国家中，原发性肝癌的发病率和病死率均呈上升趋势。 Thomas MB,et al. J Clin Oncol, 2005,23 (13): 2892-99.null背 景我国每年肝癌死亡病例占世界肝癌死亡病例的45%。 在广西，尽管各级政府采取了“改水、防霉、防肝炎”等一系列预防措施，但肝癌的发病率和病死率仍未见明显回落，肝癌年死亡率高居所有肿瘤的第一位。Thomas MB,et al. J Clin Oncol, 2005,23 (13): 2892-99.null原发性肝癌的治疗模式null肝癌的治疗方式及效果Thomas MB,Zhu AX. Hepatocellular Carcinoma: The Need for Progress. J Clin Oncol,2005,23:2892-99.null肝癌的治疗方式及效果Thomas MB,Zhu AX. Hepatocellular Carcinoma: The Need for Progress. J Clin Oncol,2005,23:2892-99.nullNCCN Practice Guidelines in Oncology – v.1 2007 Hepatocellular CarcinomanullUnresectable or patient declines surgerynullnullMetastatic diseasenullnull原发性肝癌的化疗null单药 方案 气瓶 现场处置方案 .pdf气瓶 现场处置方案 .doc见习基地管理方案.doc关于群访事件的化解方案建筑工地扬尘治理专项方案下载 在肝癌治疗中的应用nullRR5-17%,DCR30-40%,OS7.0±mGemcitabine单药Yang TS,et al. Cancer. 2000,89(4):750-6. Fuchs CS,et al. Cancer. 2002,94(12):3186-91. Kubicka S,et al. Hepatogastroenterology. 2001,48(39):783-9. 1000-1200mg/m2, iv30’,qwX3,Q4w or 10mg/min, qwX3,Q4wnullADM单药治疗肝癌的RR约为10%A new randomized phase II design for testing investigational drugs in hepatocellular carcinoma (HCC) Zee B C, Mok T S, Yeo W, Chan ATC, Johnson PJ. Chinese University of Hong Kong, Shatin, Hong Kong Special Administrative Region of China; University of Birmingham, Edgbaston, United Kingdom 对目前已发 表 关于同志近三年现实表现材料材料类招标技术评分表图表与交易pdf视力表打印pdf用图表说话 pdf 的有关文献进行评估及校正分析2007 ASCO-4205 nullPemetrexed(培美曲塞)单药治疗中晚期肝癌 无效Single-agent pemetrexed in patients with advanced and metastatic hepatoma Cohn A, Myers JW, Mamus S, Deur C, Nicol S, Hood KE, Khan AMM, Ilegbodu D, Asmar L US Oncology Research, Inc., Denver, CO; Texas Oncology PA, Austin, TX; Cancer Centers of Florida, Orlando, FL; US Oncology Research, Inc., Houston, TX 2007 ASCO-14064 nullOxa单药治疗中晚期HCC有较好效果Phase II study of oxaliplatin in patients with unresectable, metastatic or recurrent hepatocellular cancer Y. Yen, J. Doroshow, L. Leong, D. Lim, L. Wagman, R. Morgan, P. Frankel, H. Lenz, D. Gandara, S. Shibata City of Hope Comprensive Cancer Center, Duarte, CA; USC, Los Angeles, CA; UC Davis, Sacramento, CA15例HCC中,OS 10.0m,6m生存率51%2007 ASCO- 4169nullFinal results of a multicenter phase II study of irinotecan (CPT-11) in patients (pts) with advanced hepatocellular carcinoma (HCC) V. Boige, J. Taieb, M. Hebbar, E. Magherini, D. Mignard, T. Debaere, L. Hannoun, J.-M. Tigaud, M. Ducreux Institut Gustave Roussy, Villejuif, France; Laboratoire Aventis, Paris, France CPT-11 350 mg/m2, or 200 mg/m2, over 30 to 90 min, q3w. 单药CPT-11 : 疾病控制率56%nullGemcitabine联合方案 在肝癌治疗中的应用nulllevel 1 :Gem 1000 mg/m2 d1,8; Dox 30 mg/m2 d1 level 2 :Gem/Dox 1250/30 level 3 :Gem/Dox 1250/45 level 4 :Gem/Dox 1250/60. 21-day per cycleYang TS,et al. Annals of Oncology , 2002 ,13: 1771–8.Gemcitabine +恩环类null最佳剂量 Gem/Dox 1250/30 可评价 34例 PR 4 (11.8%) MR6 (17.6%) SD 9 (26.5%) PD15 (44.1%) 3/4度: 贫血(45.7%),粒细胞减少 (51.4%), 血小板减少(25.7%);其他反应轻微。 OS4.6 m,TTP2.5m.Yang TS,et al. Annals of Oncology , 2002 ,13: 1771–8.Gemcitabine +恩环类Gemcitabine +ADM对中晚期HCC有一定的疗效，但OS和TTP太短nullGemcitabine +OxaplatinnullGEMOX-1: Gem1000 mg/m2 D1,Oxa100 mg/m2 D2 GEMOX-2: Gem1500 mg/m2 D1, Oxa 85mg/m2 D1. q2w,直至进展或不能耐受PR4/22(19%),SD10/22(48%),OS12m,PFS5.0m 血小板减少 GEMOX-1 vs. GEMOX-2:18% vs.40%) 粒细胞减少 0% vs.30%. 两种用药方式疗效相当，而GEMOX-1耐受性更好。进入扩大II期研究。Gemcitabine +OxaplatinnullGemcitabine plus oxaliplatin (GEMOX) in patients with advanced hepatocellular carcinoma (HCC): results of a phase II study. Louafi S, Boige V, Ducreux M, Bonyhay L, Mansourbakht T, de Baere T, Asnacios A, 33例HCC入组。32例可评价疗效。DCR 76%(PR18%, SD58%) PFS 6.3m, OS11.5m 3/4度：血小板减少27%(例数)；粒细胞减少24%可能对延长OS有意义 GEMOX+Cetuximab 正在进行中 Cancer,2007,109(7):1384-90. Gemcitabine +OxaplatinnullGemcitabine +Oxaplatin+单抗null中位PFS达5.3m，值得进一步临床研究30例,DCR47%(PR20%,SD27%), OS9.6m,PFS5.3m 3/4度：粒细胞减少，一过性转氨酶升高cycle 1 (14 days)： Bevacizumab 10 mg/kg on day 1. cycle 2 and beyond (28 days)： Bevacizumab 10 mg/kg d1,15 Gem1,000 mg/m2 (10 mg/m2/min) d2,16 Oxa 85 mg/m2 d2,16.Gemcitabine +Oxaplatin+ bevacizumab：GEMOX-BnullA phase II study of pegylated liposomial doxorubicin (PLD) and gemcitabine (G) in the treatment of hepatocellular carcinoma (HCC) not suitable for loco-regional therapy D. Pastorelli, G. Cartei, F. Zustovich, S. Zovato, G. Artioli, R. Ceravolo, M. Nicoletto, S. Binato, M. Mattiazzi IOV- IRCCS, Padova, Italy ADM脂质体联合GEM在不适合局部治疗的HCC中， 显示较出好的效果。2007 ASCO 4585PLD 30mg/m2 IV60’ d1;GEM 1000mg/m2 d1,8 every 28 days. 直至病情进展或不能耐受毒性反应 3/4粒细胞减少:6/35例CR 2, PR 6, SD 12 ,PD 14. TTP6.2m (range 1.9–31.7+). OS: 8.8 m (range 1.9–36.5+). ADM脂质体联合GEMnull其他联合方案治疗肝癌的 临床研究nullSystemic chemotherapy with capecitabine, doxorubicin and cisplatin for metastatic hepatocellular carcinoma D. Shin, S. I. Lee, J. Park, S. H. Park, S.-M. Bang, E. K. Cho, J. H. Lee Gachon Medcl Sch Gil Medcl Ctr, Inchon, Republic of Korea RR 7例(26%),SD5例(18.5%). OS 11.6 m (95% CI, 2.2–21.0) TTP 3.7 m (95% CI, 2.0–5.5). Xeloda+ADM+DDP2007 ASCO-4177 ADM 50 mg/m2, DDP 60 mg/m2 d1, capecitabine 2,000 mg/m2/dayX 2 weeks 疗效较好，毒性反应轻Xeloda+ADM+DDPnullPreliminary results of a phase II trial of FOLFOX4 regimen in Chinese patients with unresectable primary liver cancer S. K. Qin, Y. J. Wang, Q. Wu, B. C. Xing Chinese PLA Cancer Center, Nanjing, China 2007 ASCO-14065OXA 85mg/m2 d1; LV 200mg/m2 IV 2hrs d1,2; 5-FU 400mg/m2 bolus, d1,2 and 5-FU 600mg/m2 CIV 22hrs d1,2; q2w upto 6 cycles FOLFOX4RR19.2% (5/26; 1 CR / 4 PR), DCR 57.7% (15/26; including 10 SD). 暂时无随访结果 近期疗效较好FOLFOX4nullA phase II trial of continuous-infusion 5-fluorouracil, mitoxantone and cisplatin for metastatic hepatocellular carcinoma 2007 ASCO-4081 DDP 80 mg/m2 ； mitoxantrone 6 mg/m2 on day 1, 5-FU 450 mg/m2/day d1-5. Per 4 weeks to a maximum of 6 courses Ikeda M, Okusaka T, Ueno H, Takezako,Morizane CY National Cancer Center Hospital, Tokyo, JapanDDP + Mitoxantrone +5-FU14/51 PR(27%) 中位缓解期7.6m (range, 2.3 to 18.4). 27/51 (53%)SD 9/51PD (18%) OS11.6 m,1年生存率44.5. 耐受性好，疗效较好DDP + Mitoxantrone +5-FUnullA phase III study of doxorubicin (A) versus cisplatin (P)/ interferon-2b (I)/ doxorubicin (A)/ fluorouracil (F) combination chemotherapy (PIAF) for inoperable hepatocellular carcinoma (HCC) 2007 ASCO-4026 W. Yeo, B. Zee, W. T. Leung, W. Y. Lau, T. S. K. Mok, H. T. M. Wong, J. Koh, S. Yu, A. T. C. Chan, P. J. Johnson Chinese University of Hong KongADM 单药与 ADM+5-Fu+干扰素-2b比较： 疗效无显著性差异ADM+5-Fu+干扰素nullV. Boige, J.-L. Raoul, J.-P. Pignon, O. Bouche, E. Boucher, J.-F. Blanc, J.-F. Seitz Gustave Roussy Institute, Villejuif, France; Eugène Marquis Ctr, Rennes, France2007 ASCO-4128 Capecitabine 2000 mg/m2,d1-14, Oxaliplatine 130 mg/m2, iv2h,d1. q3w 入组50例,35例可评价疗效: PR4, SD24 。 6ms生存率：55% 3/4度：腹泻,粒细胞缺乏,感染。治疗相关死亡2例。Preliminary results of capecitabine - oxaliplatin (XELOX) in hepatocellular carcinoma (HCC): A phase II trial of the FFCD 2003–03 trial有较好的疾病控制率，但毒性反应大。Xeloda+Oxa:XELOXnull小 结null原发性肝癌是对化疗有一定敏感性的肿瘤； 目前尚无可靠的多中心、前瞻性、随机对照的研究结果证实化疗对延长晚期肝癌患者的生存期有益。 对于有化疗适应症的中晚期肝癌，进行单药或联合方案的临床研究均符合NCCN指引。小结null4.GEM,Xeloda,OXA或脂质体ADM 的二联/三联方案在一些临床研究已观察到一定的疗效。但已有的研究入组病例数太少，结果还待验证。 5.分子靶向药物在肝癌治疗中的应用是近年来的研究热点，其中Sorafenib是目前唯一一个被证实能改善晚期肝癌生存期的药物（与安慰剂比较）。分子靶向药物与化疗药物联合在肝癌治疗中的应用值得深入研究。小结nullnull正如AJCC专家们所说的： 开展 设计 领导形象设计圆作业设计ao工艺污水处理厂设计附属工程施工组织设计清扫机器人结构设计 合理、实施过程受到严格监控的多中心临床研究是肝癌药物治疗研究中最迫切的工作。谢 谢！谢 谢！