2010nccn晚期胃癌内科治疗进展徐瑞华中山肿瘤医院精选
晚期胃癌内科治疗进展,Rui-hua Xu (徐瑞华） Sun Yat-sen University Cancer Center xurhmail.sysu.edu.cn Tel: 020-8734 3468,百家争鸣与中西合璧,中国是胃癌的高发地区,WHO统计数据显示: 胃癌所致死亡率在我国位居恶性肿瘤第三位大高,2005年我国男性十大癌症死亡率 2005年我国女性十大癌症死亡率,肿瘤分类,肺癌 胃癌 肝癌 食管癌 结直肠癌 乳腺癌 子宫癌 白血病 脑瘤 宫颈癌,肿瘤分类,死亡标率（/10万) 死亡标率（/10万),肺癌 肝癌 胃癌 食管癌 结直肠癌 白血病 脑瘤 胰腺癌 膀胱癌 鼻咽癌,我国/期胃癌患者占总胃癌患者超过60%,J Surg Concepts Pract 2008, Vol.13, No.1：24,上海市胃癌发病流行现况,胃癌治疗有效的化疗药物,Old Drugs Fluoropyrimidines 5-FU Platinum Cisplatin Anthracyclines Doxorubicin Epirubicin Etoposide Methotrexate,New Drugs Fluoropyrimidines Capecitabine S-1 Platinum Oxaliplatin Taxanes Paclitaxel Docetaxel Irinotecan,FP vs FAM vs UFTM: JCOG 9912 trial,Ohtsu et al 2003,FP 5-FU UFTM p value,No. Patients 105 105 70,Response (%) 34.8 11.4 8.6 0.0001,PFS (weeks) 3.9 1.9 2.4 0.001,MS (weeks) 7.1 7.3 6.0 NS,UFTM, tegafur uracil / mitomycin,Waters et al 1999,ECF vs FAMTX: UK Trial,Chemotherapy for gastric cancer in the past,FP regimen has been the standard or reference regimen in Asia ECF is recommended mostly in Europe,Where we have been in AGC 我们所知道的胃癌化疗,Eloxatin: REAL-2, phase III Xeloda: ML17032, phase III Taxotere: TAX 325, phase III CPT-11 V306, phase III Eloxatin: FLO vs FLP, phase III S1: JCOG 9912, phase III S1: SPIRITS, phase III 2008 ASCO DC vs FLP phase III 2009 ASCO FLAG phase III 2009 ASCO ToGO phase III 2010 ASCO AVAGAST phase III,Gastric Cancer Chemotherapy,Oxaliplatin + Capecitabine: Non inferior (REAL-2) Docetaxel + CF CF: toxicity (TAX 325) Irinotecan + CIV 5-FU = CF: less toxicity (V306) DDP + Xeloda: Non inferior, better tolorance (ML 17032) Doublets: Platin: + Irinotecan or Taxane or Fluor Fluor: + Irinotecan or Taxane or Platin,Phase III Trial in AGC with 5Fu/LV Plus Either oxaliplatin or Cisplatin (FLO vs FLP),R A N D O M I S A T I O N,FLP Cisplatin 50mg/m2 D1,15,29 FA 200mg/m2 + 5-FU 2000mg/m2 d1,8,15,22,29,36 Qd50,FLO Oxaliplatin 85mg/m2 + FA 200mg/m2+ 5-FU 2600mg/m2 24h D1,15,29,43 Qd57,Metastatic Locally advanced gastric or GEJ cancer PS2,n=112,n=106,Al-Batran. J Clin Oncol 2008; 26(9),Best Overall Response (ITT),FLO vs. FLP 治疗效果,time to treatment failure (TTF),progression-free survival (PFS),overall survival(OS),上图：全体患者；下图：年龄65岁患者,Grade ¾ Hematological and Neurosensory toxicities,- Center - PS - Unresectable vs recurent, adj Crx vs recurrent, no adj Crx,R A N D O M I S A T I O N,ARM A (Control) 5-FU civ 800 mg/m2 D1-5 q 4 weeks,ARM B S-1 80 mg/m2 D1 - 28 q 6 weeks,U N T I L P D,Primary endpoint: Overall survival A vs B: non-inferiority, A vs C: superiority,ARM C CPT-11 70 mg/m2 D1,15 CDDP 80 mg/m2 D1 q 4 weeks,JCOG 9912 Trial,Boku N, et al. Proc Am Soc Clin Oncol 2007 (#4513),JCOG 9912 Trial; Results,Boku N, et al. Proc Am Soc Clin Oncol 2007 (#4513),R A N D O M I S A T I O N,ARM A S-1 40-60 mg bid for 28 d q 6 weeks,ARM B Cisplatin 60 mg/m2 on D8 S-1 40-60mg bid for 21 d q 5 weeks,U N T I L P D,Primary endpoint: Overall survival (Superiority),Center PS Unresectable vs. recurrent,SPIRITS Trial,Narahara H et al. ASCO 2007,Results of SPRITS Trial,Narahara H et al. ASCO 2007,Country: 23 (US, Europe, South America, Ukraine) Primary Endpoint: Overall survival (Superiority) Patient accrual 1050 (completed in March, 2007),FLAGS Trial (First-Line Advanced Gastric Cancer Study),Type of disease (Locally advanced vs Metastatic 1 metastasis vs Metastatic 1 metastases) - Prior adjuvant CT Measurable disease - Centers,Cisplatin 75 mg/m2 IV Day 1,S-1 25mg/m2 bid po Day 1-21,Cycles repeated every 4 weeks,Cisplatin 100 mg/m2 IV Day 1,Cycles repeated every 4 weeks,5-FU 1000 mg/m2/day CIV Day 1-5 (over 120 hours ),521,479,402,341,276,212,172,124,90,79,69,55,48,44,36,32,24,19,14,8,6,4,4,2,0,0,508,452,385,326,250,199,156,116,79,67,56,48,35,27,26,21,19,14,12,8,8,4,3,3,1,0,Months From Randomization,% Survival,N at Risk,S-1:,5-FU:,CS,CF,0,10,20,30,40,50,60,70,80,90,100,0,1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,Log-rank Test: p = 0.1983 Hazard Ratio: 0.92 (95% CI: 0.80, 1.05) Median Overall Survival: CS: 8.6 months CF: 7.9 months,FLAGS: PFS,Ajani, et al. ASCO GI 2009,% 无进展生存率,100 90 80 70 60 50 40 30 20 10 0,Log-rank Test: p=0.9158 相对危险度: 0.99 (95% CI: 0.86, 1.14) CS: 4.8 months CF: 5.5 months CS （顺铂/S1） CF （顺铂/5-Fu）,0,2,4,6,8,10,12,14,16,18,20,22,24,26,28,521,365,237,152,91,41,24,17,12,9,8,5,1,0,508,335,235,149,75,36,22,16,11,6,4,N at risk S-1: 5-FU:,随机后时间（月）,临床反应率比较（可评估的ORR）,a Fisher确切检验 （双侧）,*,*,*,* P0.01,0,10,20,30,40,50,60,70,Anemia,Neutropenia,Thrombocytopenia,Leukopenia,Febrile neutropenia*,* Patients with febrile neutropenia or neutropenic infection,*,CS,CF,Percentage of patients (%),Grade 3-4 Hematologic
