胃癌的輔助治療新認(rèn)識(shí)

1、1,胃癌的輔助治療新認(rèn)識(shí)(第11屆CSCO 上海),南昌大學(xué)第一附屬醫(yī)院 熊建萍2008年08月29日,2,流行病學(xué):發(fā)病及死亡位次,,New Cases(rank) Deaths(rank),1 Jemal,et.al.CA Cancer J Clin 2007;57:432 Parkin,et.al.CA Cancer J Clin 2005;55:75,3,流行病學(xué)：發(fā)病率及部位超勢(shì),Epidemiologic Tre

2、ndsWorldwide decline in age-adjusted incidence now parallels pattern previously observed in United StatesDisease now appearing anatomically in a more proximal pattern,4,,,5,部分國(guó)家胃癌發(fā)生部位,Percentage,1. Yang H, et al. Cance

3、r Res Treat 2001;33:207–15; 2. Inoue, et al. Int J Cancer 1994;56:494–93; 3. Hundalh S, et al. Cancer 2000;88:921–2; 4. Siewert J, et al. Ann Surg 1998;228:449–61; 5. Bonenkamp J, et al. N Engl J Med 340;908–14,1,2,5,4

4、,3,,,6,胃癌 5年生存率 （中國(guó)）,時(shí)期 例數(shù) Ⅰ Ⅱ Ⅲ Ⅳ 總體~1975 714 85.7 47.8 27.6 0 23.7 1976~85 2615 88.7 62.5 28.9 8.0 35.91986~ 3520 90.4

5、 67.9 36.7 8.6 45.6,,7,胃癌的臨床特點(diǎn),診斷時(shí)發(fā)生轉(zhuǎn)移率高>50%可手術(shù)患者術(shù)后復(fù)發(fā)率高晚期患者中位生存期短(3~4月) 總體治愈率低如何提高胃癌的治愈率?,8,重視早期患者的綜合治療,術(shù)前輔助化療(新輔助化療)術(shù)后輔助化療及輔助化放療降低復(fù)發(fā)率 提高治愈率!,,9,新輔助化療的目的,縮小原發(fā)腫瘤的體積，并減少手術(shù)切除的難度，增加手術(shù)安全性與有效性全身早期治療消滅微小的轉(zhuǎn)

6、移病灶，防止腫瘤的復(fù)發(fā)與轉(zhuǎn)移,10,新輔助化療的種類,不可手術(shù)患者通過(guò)降期提高手術(shù)切除率可手術(shù)患者先期用藥消除隱匿性微轉(zhuǎn)移灶 減少術(shù)后復(fù)發(fā)轉(zhuǎn)移,11,不可手術(shù)患者通過(guò)降期提高手術(shù)切除率,1989年Wilke Ⅱ期臨床研究 無(wú)法切除的34例胃癌 EAP 2～4療程方案化療 結(jié)果70%有效 20例獲得Ⅱ期手術(shù)

7、切除 10例達(dá)R0切除,12,不可手術(shù)患者通過(guò)降期提高手術(shù)切除率,1995年Wilke總結(jié)了西歐10組共196例 無(wú)法切除胃癌病人的術(shù)前化療 認(rèn)為能使近50%的晚期胃癌降期 獲得手術(shù)切除甚至R0切除 對(duì)延長(zhǎng)生存期有積極作用,尚缺少Ш期臨床研究證據(jù),13,新輔助化療的種類,不可手術(shù)患者通過(guò)降期提

8、高手術(shù)切除率可手術(shù)患者先期用藥消除隱匿性微轉(zhuǎn)移灶 減少術(shù)后復(fù)發(fā)轉(zhuǎn)移,,14,,,可手術(shù)患者的Ш期臨床研究,CSC n=250,S n=253,R,,開(kāi)始術(shù)前化療 (ECF)n=237 (95%),,,完成術(shù)前化療 (ECF)n=215 (86%),,進(jìn)行手術(shù)n=219 (88%),進(jìn)行手術(shù)n=240 (95%),Cunningham et al, N Engl J Med 2006;355:11-20.,,(MAGI

9、C 研究),ECF:E 50mg/m2C 60mg/m2FU 200mg/m2/d civ,15,MAGIC: 術(shù)前化療可降期,16,MAGIC: 術(shù)前化療可提高R0切除率,17,,,,MAGIC: 術(shù)前化療能延長(zhǎng)無(wú)復(fù)發(fā)生存及總生存期,,,18,,,,,,MAGIC: 術(shù)前化療能延長(zhǎng)長(zhǎng)期生存率 術(shù)后并發(fā)癥相同,19,,,MAGIC: 術(shù)前化療對(duì)各部位原發(fā)腫瘤均有益,20,MAGIC: Preoperative ECF vs. S

10、urgery alone,術(shù)前ECF能使腫瘤降期術(shù)前ECF可提高R0切除率術(shù)前ECF能延長(zhǎng)生存期,21,,,,可手術(shù)患者的隨機(jī)臨床研究,22,,FFCD 9703:研究方案設(shè)計(jì),23,,,FFCD 9703: 入選標(biāo)準(zhǔn),,24,,,,FFCD 9703: 病人特征,,25,,,,FFCD 9703:術(shù)前化療的近期療效,,,26,FFCD 9703:術(shù)前化療的外科及病理結(jié)果,,27,FFCD 9703: 5年DFS及OS均有提高,,,

11、28,,,FFCD 9703: 術(shù)前化療組毒性反應(yīng),29,,,FFCD 9703: 結(jié)論,30,新輔助化療的優(yōu)點(diǎn),不可手術(shù)患者通過(guò)降期提高手術(shù)切除率（尚需要進(jìn)行Ш期臨床研究）可手術(shù)患者早期用藥可能消除隱匿性微轉(zhuǎn)移灶減少術(shù)后復(fù)發(fā)轉(zhuǎn)移腫瘤血管未被手術(shù)破壞，可增強(qiáng)化療效果可迅速緩解梗阻疼痛等腫瘤相關(guān)癥狀根據(jù)臨床和病理療效了解是否對(duì)化療敏感，指導(dǎo)術(shù)后合理的治療方式,31,重視早期患者的綜合治療,術(shù)前輔助化療(新輔助化療)術(shù)后輔助化療

12、及輔助化放療降低復(fù)發(fā)率 提高治愈率!,,32,,,東西方國(guó)家胃癌術(shù)后局部復(fù)發(fā)率,1,2,4,4,3,16,12,38,29,19,1Lee et al 2000; 2Maruyama et al 1998;3Landry et al 1991; 4Macdonald et al 2001,Patients (%),D2,D2,54%,36%,10%,D0:,D1:,D2:,LN dissection,33,Presenter: D

13、r. F. De Vita,Surgery plus ELFE (epirubicin, leucovorin, 5-fluorouracil and etoposide) vs surgery alone in radically resected gastric cancer : Final results of a randomised phase III trial by the Gruppo Oncologico Ital

14、ia Meridionale (GOIM),2006 ASCO,34,GOIM9602: 研究方案設(shè)計(jì),Radically resected gastric cancer,Nodal Status (N-/N+),R,SURGERY +ELFE,SURGERY,FOLLOW-UP EVERY 12 WEEKS,ELFE ×6EPI 60 mg/m2 IV D1LV 100 mg/m2 IV D1-5

15、5-FU 375 mg/m2 IV D1-5VP-16 100 mg/m2 IV D1-3 Every 3 Weeks,,,,,,,,,35,PATIENT POPULATION,組織學(xué)證實(shí)的胃及胃-食管聯(lián)合部腺癌Lymph node metastases (N1 or N2) and/or serosa invasion (pT3) or extension to adjacent organs (pT

16、4) according to AJCC staging of 1992年齡 ≤70 years合適的骨髓、肝腎、心臟功能ECOG performance status 0-2手術(shù)后6周內(nèi)開(kāi)始化療知情同意,SURGERY PRODCEDURES,R0 resection (total or subtotal gastrectomy and D1 lymphoadenectomy),GOIM9602: Entry criteri

17、a,36,GOIM9602 :Drug delivery,Total number of cycles 638Median number 5 (1-6),CT STOP 18%,61% of pts full dose CT39% of pts dose reduction,37,GOIM 9602: Survival Result,,5-YearResult,LogRank,HR(95%CI),

18、Surgery+FLFE,Surgery,OS 48% 43.5% p=0.610 0.91(0.69,1.21)DFS 44% 39% p=0.305 0.88(0.78,0.91)OS/N+ 41% 34%

19、 P=0.068 0.84(0.69,1.01)DFS/N+ 39% 31% P=0.050 0.86(0.75,1.00),,In multivariate Cox proportional hazard ratio analysis.Treatment was not a signifinant predictor for risk of deat

20、h.HR 0.91(95% CI 0.69,1.21), P=0.610,,38,GOIM 9602: Toxicity of CT (WHO),39,本研究不能證明術(shù)后輔助化療對(duì)生存有益需要使用現(xiàn)代的新的有效藥物進(jìn)行術(shù)后輔助治療的臨床研究,GOIM 9602: Conclusions,40,術(shù)后輔助化療與單純手術(shù)的臨床研究結(jié)果,,41,近年術(shù)后輔助化療Meta分析總結(jié),,42,對(duì)于術(shù)后輔助化療的認(rèn)識(shí),Meta分析微小的生存益處而

21、單個(gè)臨床研究結(jié)果未顯出優(yōu)勢(shì)？ 入組的病例數(shù)較少 化療方案客觀有效率不高新一代有效率高的化療藥物及方案應(yīng)該用于胃癌的術(shù)后輔助化療研究,43,S-1(替吉奧膠丸)Phase II 1st line,.,,,,,,44,,,2007 ASCO Gl Cancers Symposium Abstr 8,ACTS-GC,45,ACTS-GC:方案設(shè)計(jì),,ACTS-GC:方案設(shè)計(jì),46,,,ACTS-GC:病

22、人特征,,,47,,,ACTS-GC:S1完成情況,,48,,,ACTS-GC:不良反應(yīng),,49,,,,ACTS-GC:總生存率有差異(P=0.0024) 無(wú)復(fù)發(fā)生存率差異明顯(P<0.0001),,50,,,,ACTS-GC:各亞組分析均有生存優(yōu)勢(shì),,性別、年齡,臨床分期、T分期,N分期,51,,,新藥術(shù)后輔助化療結(jié)果令人鼓舞術(shù)后輔助化放療證據(jù)可靠！,ACTS-GC:結(jié)論,52,53,54,,

23、,55,56,結(jié)論：術(shù)后輔助化放療降低D2 術(shù)后病人局部復(fù)發(fā)率,韓國(guó)的文獻(xiàn)綜述,,,57,胃癌輔助治療仍然存在爭(zhēng)論,術(shù)前及術(shù)后ECF方案被NCCN推薦術(shù)后輔助化放療成為美國(guó)的標(biāo)準(zhǔn)治療日本S1研究得到陽(yáng)性結(jié)果(ACTS-GC study) The GOIM9602（FLFE方案）不支持術(shù)后化療需要Phase Ⅲ trials 評(píng)價(jià)理想的化療方案和選擇化療與手術(shù)及放療的關(guān)系,58,正在進(jìn)行的Phase III adjuv

24、ant trials in gastric cancer,,,59,a long way to go,1. Van Cutsem E, et al. J Clin Oncol. 2006,24:4991-4997.2. Goldberg R, et al. J Clin Oncol 2004;22:23–30.3. de Gramont A, et al. J Clin Oncol 2000;18:2938–2947.,60,謝謝