1、医学课件1今天的主要内容O 食管癌分期的争议与进展食管癌分期的争议与进展 (第六第六,七版七版)O 食管癌外科进展食管癌外科进展O 食管癌化疗进展食管癌化疗进展医学课件2分期的变化与争议分期的变化与争议医学课件36th Edition 6th Edition AJCC AJCC Cancer StagingCancer Staging-1977-1977医学课件4食管癌分期(UICC/AJCCUICC/AJCC,19971997)OM M更明确的界定更明确的界定OMX, M1MX, M1进一步分进一步分M1aM1a、M1bM1b 部位部位 M1a M1b M1a M1b 胸上段胸上段 颈部颈部
2、LNM LNM 其余远处转移其余远处转移 胸中段胸中段 不应用不应用 非区域非区域LNMLNM或远处转移或远处转移 胸下段胸下段 腹腔动脉腹腔动脉LNM LNM 其余远处转移其余远处转移医学课件5医学课件6医学课件7医学课件8 食管癌分期(UICC,1997) Stage Grouping Stage0 Tis N0 M0 Stage T1 N0 M0 StageA T2 N0 M0 T3 N0 M0 StageB T1 N1 M0 T2 N1 M0 Stage T3 N1 M0 T4 Any N M0 Stage Any T Any N M1 StageA Any T Any N M1a S
3、tageB Any T Any N M1b医学课件9AJCC/UICCAJCC/UICC分期的指导思想O强调肿瘤侵润深度(而非长度)对分期的影响强调肿瘤侵润深度(而非长度)对分期的影响O强调非区域性淋巴结转移对分期的影响,将非区强调非区域性淋巴结转移对分期的影响,将非区域性淋巴结转移归属于域性淋巴结转移归属于M1M1而非而非N2 N2 (等同内脏器官(等同内脏器官转移)转移)O以日本食管癌临床研究资料为基础制订(颈、胸以日本食管癌临床研究资料为基础制订(颈、胸段食管鳞癌为主)段食管鳞癌为主)医学课件10存在的主要争议O未将胃未将胃- -食管连接部肿瘤包括在内,故受到食管连接部肿瘤包括在内,故受
4、到以胃以胃- -食管连接部腺癌为主要食管癌的大部食管连接部腺癌为主要食管癌的大部分欧美国家的质疑。分欧美国家的质疑。OT3T3、T4T4同归为同归为期,等于认同期,等于认同T3T3、T4T4对患者对患者远期生存没有影响。远期生存没有影响。O区域性淋巴结的划分受质疑。区域性淋巴结的划分受质疑。O淋巴结转移数量对愈后的影响未纳入淋巴结转移数量对愈后的影响未纳入医学课件11 KORSTKORST分期,19981998-二种分期区域淋巴结的比较二种分期区域淋巴结的比较医学课件12-Krost分期区域淋巴结划分分期区域淋巴结划分医学课件13-T分期对愈后的影响(分期对愈后的影响(T3、T4)医学课件14
5、-淋巴结转移数量与愈后的关系淋巴结转移数量与愈后的关系医学课件15-T分期与淋巴结转移的关系分期与淋巴结转移的关系医学课件16医学课件17-澳大利亚弗林德斯大学对不同分期食管腺癌与生存的研究(澳大利亚弗林德斯大学对不同分期食管腺癌与生存的研究(b)医学课件18医学课件197th Edition 7th Edition AJCC AJCC Cancer StagingCancer Staging-2009-2009医学课件20修订的依据O20062006年,年,AJCCAJCC主持主持 World wide Esophageal World wide Esophageal Cancer Coll
6、aborationCancer Collaboration(WECC)WECC)O共共1313个机构参加个机构参加O收集收集78857885例,最终入组例,最终入组46284628例单纯手术患者例单纯手术患者医学课件21 WECCWECC协作单位 医学课件22 患者临床病理资料医学课件23 患者临床病理资料医学课件24修改要点O 添加新元素:添加新元素:Histological TypeHistological TypeGrade of DifferenciationGrade of DifferenciationO 修改旧元素:修改旧元素:T T:细分:细分T1T1与与T4T4N N:转移淋
7、巴结个数:转移淋巴结个数M M:取消:取消M1aM1a和和M1bM1bStagingStaging医学课件25T T分期医学课件26N N分期医学课件27M M分期医学课件28H H G G医学课件29StagingStagingII期III期 IIaIIbIIIIIIIIaIIIb医学课件30局限性O仅适用于单纯手术患者仅适用于单纯手术患者O不适用于非手术治疗患者不适用于非手术治疗患者O对对T4bT4b及及M1M1患者的代表性差患者的代表性差O不包括颈段食管癌不包括颈段食管癌O未应用未应用T1aT1a与与T1bT1bO取消取消M1aM1a医学课件31外科治疗进展外科治疗进展医学课件32 目前
8、外科治疗效果O 切除率切除率 58589292O 并发症发生率并发症发生率 6.36.320.520.5O 3030日死亡率日死亡率 2.32.35.05.0O 5 5年生存率年生存率 8 83030O 1010年生存率年生存率 5.25.22424 张汝刚:食管癌的综合治疗;张汝刚:食管癌的综合治疗;2005;8医学课件33 食管癌外科治疗结果 作者作者 年代年代 病例数病例数 5-Sur (%) 5-Sur (%) 手术死亡率手术死亡率 Earlam 1980 83783 15 29 Earlam 1980 83783 15 29 Muller 1990 76911 10 13Muller
9、 1990 76911 10 13邵令方邵令方 1993 60000 25-40 2.8-4.1 1993 60000 25-40 2.8-4.1张汝刚张汝刚 1998 4538 29.9 3.5 1998 4538 29.9 3.5刘志才刘志才 1999 3867 33.7 0.78 1999 3867 33.7 0.78戎铁华戎铁华 2000 2041 25.2 1.2 2000 2041 25.2 1.2O 综述综述 * *中国医科院肿瘤医院中国医科院肿瘤医院 # # 林州市食管癌医院林州市食管癌医院医学课件34早期食管癌的治疗EEMREEMR (1993, Makuuchi H et
10、al, Japan) (1993, Makuuchi H et al, Japan)1. 1. 准确判定是上皮内癌,无准确判定是上皮内癌,无LNMLNM2. 2. 术前准确判定病灶范围、术后判定切除彻底性术前准确判定病灶范围、术后判定切除彻底性3. 3. 可获得术后随访及辅助治疗可获得术后随访及辅助治疗 但但YokoyamaYokoyama等认为,如侵犯粘膜肌层可等认为,如侵犯粘膜肌层可EEMREEMRRT/CTRT/CT医学课件35早期食管癌的治疗EEMREEMR 日本日本Makuuchi -HMakuuchi -H等等(1999) (1999) 246 246例例 5-y SR 100%
11、5-y SR 100%国内王国清等(国内王国清等(19991999) 154 154例,穿孔例,穿孔2 2例,出血例,出血1818例,例,3 3年生存率年生存率 100% 100%、1 1年内复发率年内复发率10%10%,再次治疗满意。,再次治疗满意。 治疗原位癌、黏膜内癌、癌前病变的重要手段治疗原位癌、黏膜内癌、癌前病变的重要手段 并发症:出血,穿孔并发症:出血,穿孔医学课件36争议50%变为原位癌25%变为原位癌10%变为原位癌EMRFOLLOW UP延误延误治疗治疗治疗治疗过度过度医学课件37早期食管癌的治疗 食管切除及LNDLND作者作者 邵令方邵令方 常扶保常扶保 陆士新陆士新 (1
12、996) (1998) (1999) 例数例数 208 298 3185 -y 92.6%86.2% 89.9%10-y 71.6%72.6% 72.6%15-y 62.7%58.2% 58.2%20-y 50.9%38.6% 38.2% 医学课件38医学课件39医学课件40医学课件41医学课件42医学课件43结论O胸腔镜辅助下食管癌切除术是安全可行的胸腔镜辅助下食管癌切除术是安全可行的O对对-期的患者其愈后是满意的期的患者其愈后是满意的O手术时间及淋巴结清扫可以经过训练后改善手术时间及淋巴结清扫可以经过训练后改善O仍需随机对照研究仍需随机对照研究医学课件44化疗进展化疗进展医学课件45单药对
13、食管癌的疗效(Ajani 1994)Ajani 1994) 药药 物物可可 评评 例例 数数有效率(有效率(% %) Fluorouracil (5Fu)3915 (38.5) Methotrexate (MTX)7025 (36) Mitomycin C (MMC)3311 (33) Bleomycin (BLM)8124 (30) Vindesine (VDS)8419 (26) Cisplatin (PDD)23156 (24) Mitoquazone (MGAG)6415 (23) Adrimycin (ADM)387 (18.4) Lomustin (CCNU)193 (16) Tr
14、imetrexate (TMTX)243 (12.5) Carboplatin (CBP)302 (6.6) Ifosphamide (IFO)322 (6.3) Navelbine (NVB)246 (25) Paclitaxel (Tax)5116 (32)医学课件46食管癌联合化疗 联联 合合 方方 案案可评例数可评例数有效例数(有效例数(%) 中数有效期中数有效期(m)PDD+BLM619(15)6BLM+ADM163(19)4PDD+VDS+BLM68 36(53)7PDD+MTX+BLM105(50)7PDD+ADM+5FU217(33)-PDD+BLM+VP-16165(31)-
15、PDD+5FU142 87(61)8PDD+VDS+MGAG136(46)-PDDBLMMTXMGAG149(64)-PDDVCRBLM5FU106(60)-医学课件47PDD+5FUPDD+5FU治疗食管癌研究者研究者PDD (mg/m2)5FU (mg/m2/d)例数例数有效率有效率(%)MS(月)月)Hellerstein(1982)100,d11000,d1-5108(80)-Kies(1987)同上同上同上同上2611(42)17.8Hilgenberg(1988)同上同上1000,d1-43520(57)-Carey(1993)100,d11000,d1-47045(66) Wri
16、ght(1994)100,d11000,d1-5166(37)Ajani(1994)同上同上同上同上14287(61)医学课件48食管癌: TaxanesTaxanes化疗 方方 案案病理类型病理类型例例 数数有效率(有效率(%)Paclitaxel 24h鳞癌鳞癌2028腺癌腺癌3034Paclitaxel 1h 鳞鳞+腺腺4117Docetaxel腺癌腺癌825P(3h)+DDP/5FU鳞癌鳞癌3050腺癌腺癌3046P(3h)+DDP/5FU 鳞鳞+腺腺1770P(24h)+DDP 鳞鳞+腺腺3244P+DDP,Q2W 鳞鳞+腺腺2040P+DDP,Q2W 鳞鳞+腺腺5852P+CBP腺
17、癌腺癌944医学课件49Single Agent Taxanes in Metastatic Esophageal CancerAuthor Drug/Dose #Pts. Prior Rx CR(%) PR(%) Med Surv.(mo)Kelsen P/80qw 65 Y 0 14.5 6.5Ajani P/250 50 N 2 30 13.2Ohtsu D/7049 Y 0 25NR 医学课件50 Taxanes Taxanes 是由太平洋紫杉树或红豆杉的树干、是由太平洋紫杉树或红豆杉的树干、树皮或针叶中提取或半合成的一类抗肿瘤植物药树皮或针叶中提取或半合成的一类抗肿瘤植物药 作用机理
18、主要是促进微管聚合从而抑制了细作用机理主要是促进微管聚合从而抑制了细胞分裂,导致癌细胞死亡胞分裂,导致癌细胞死亡 目前在临床上应用的紫杉醇类药物主要有两目前在临床上应用的紫杉醇类药物主要有两种:种:PaclitaxelPaclitaxel和和DocetaxelDocetaxel医学课件51J Ajani M. D. Anderson Cancer Center医学课件52J Ajani M. D. Anderson Cancer CenterO19941994首先报道单药首先报道单药TaxolTaxol治疗食管腺、鳞癌有效治疗食管腺、鳞癌有效 -J Natl Cancer Inst-J Nat
19、l Cancer Inst,1994;86(14):1086-911994;86(14):1086-91O19951995报道报道TaxolTaxol单药对食管、贲门癌疗效突出,单药对食管、贲门癌疗效突出,耐受性良好耐受性良好.RR.RR:36% 36% 。 -Semin Oncol -Semin Oncol ,1995 ; 22(3 Suppl 6):35-401995 ; 22(3 Suppl 6):35-40O19961996报道联合方案:报道联合方案:TPFTPF方案方案Taxol 175mg/ mTaxol 175mg/ m2 2,d1d1;PDD 20 mg/ mPDD 20 mg
20、/ m2 2/d/d,静滴,静滴,d1-5d1-5;5-Fu 750 5-Fu 750 mg/ mmg/ m2 2/d/d,d1-5d1-5,2828天天/C .RR/C .RR:45% 45% -Semin Oncol -Semin Oncol ,1996 ;23(5 Suppl 12):55-81996 ;23(5 Suppl 12):55-8 医学课件53O 1996 Ilson TPF RR1996 Ilson TPF RR:48%48% Oncology (Huntingt)Oncology (Huntingt), 1996;10(9):1385-961996;10(9):1385-
21、96. .O 1998 Petrasch TP RR1998 Petrasch TP RR:40%40% Br J Cancer Br J Cancer ,1998;78(4):511-41998;78(4):511-4. .O 1998 Kelsen TP RR1998 Kelsen TP RR:49%49% J Clin Oncol J Clin Oncol ,1998 ;16(5):1826-341998 ;16(5):1826-34 医学课件54Phase II multicenter trial of Phase II multicenter trial of docetaxel +
22、 oxaliplatin in docetaxel + oxaliplatin in stage IV gastroesophageal stage IV gastroesophageal and/or stomach cancerand/or stomach cancerO Richards DA et al.医学课件55Study designStudy designPATIENT PROFILE: Median age=59.4 years 72% male patients, 76% white ECOG PS scores: 0 (45%); 1 ( 49%); 2 (6%) 32.
23、8% of patients had distal gastric cancerN=71Eligibility:Patients with metastatic (Stage IV) AGEJ/SENDPOINTS: Primary: ORR, Secondary: time to response, duration of response, TTP, toxicity, 1- and 2-year survivalDocetaxel60 mg/m2 1h IV D1; q3wOxaliplatin130 mg/m2 2h IV D1; q3w+医学课件56Results: efficacy
24、Results: efficacyN%Best responsePartial response25 38Stable disease (SD 6 months; 3 patients)3452Progressive disease711Clinical benefit rate2842Time to response (months) Median 1.3 Range 1.14.4Duration of response (months) Median 4.6 Range 2.718.3Estimated overall survival rate Media survival time 9
25、5% CI 9.2 months 6.511.2RR of 38% similar to TAX 325; OS of 9.2 months similar to TAX 325医学课件57Adverse events (Grade 3/4)Total (%)Haematological Leukopenia Neutropenia Thrombocytopenia Febrile neutropenia177077Non-haematological Dehydration Diarrhoea Fatigue Nausea Vomiting1313131617Results: toxicit
26、y医学课件58Authors conclusionsAuthors conclusionsOThe combination of oxaliplatin and docetaxel is well tolerated in patients with Stage IV GEJ/gastric cancerOThe most frequent toxicity is haematological with 70% of the patients developing Grade 34 neutropenia. OFebrile neutropenia episodes were infreque
27、nt, occurring in 7% of patientsOThe combination of oxaliplatin and docetaxel produces an encouraging confirmed response rate of 38% and a clinical benefit rate of 42%, which are comparable to other standard front-line regimens This combination deserves further study in Phase III investigations医学课件59
28、Key messagesKey messagesOThe median survival time (9.2 months) is consistent with the TAX 325 resultsThis study confirms: The safety of combining docetaxel and oxaliplatin Febrile neutropenia in 7% of patients The efficacy of this combination RR=38% Clinical benefit rate=42%Combining docetaxel and o
29、xaliplatin is a promising combination for gastric cancer医学课件60Randomised phase II study Randomised phase II study evaluating weekly docetaxel in evaluating weekly docetaxel in combination with cisplatin and combination with cisplatin and 5FU or capecitabine in 5FU or capecitabine in metastatic oesop
30、hago-gastric metastatic oesophago-gastric cancercancerO Tebbutt N, et al.医学课件61Study designStudy design N=79Evaluable N=68Inclusion criteria Metastatic oesophageal or gastric (OG) carcinoma, measurable disease PS 02RTCFDocetaxel Cisplatin5-FUPATIENT PROFILE: 100% PS 01, adequate organ function, no p
31、rior treatment, informed consent30 mg/m2 D1, D8; qw60 mg/m2 D1; q3w200 mg/m2/D continuously q3wwTCFwTXTXDocetaxelCapecitabine30 mg/m2 D1, D8; qw1600 mg/m2/D D114 q3w医学课件62ResultsResultsEFFICACYwTCFwTXConfirmed CR, % 95% CI0 0103 0.515Confirmed PR, % 95% CI44 296118 835Confirmed CR/PR, % 95% CI44 296
32、120 1037Median PFS (months)5.53.7GRADE 3/4 TOXICITYwTCF (n=35)wTX (n=35)Diarrhoea, %93Hand-foot syndrome*, %63Febrile neutropenia, %60*High dose of 5-FU (200 mg/m2/D continuous infusion for 21 days)医学课件63Authors conclusionsAuthors conclusionsOBoth wTCF and wTX are active regimensOwTCF achieves high
33、response rates and progression-free survival times comparable to 3-weekly TCF. wTCF has a more favourable safety profile and a lower rate of febrile neutropeniaOwTX has significant activity with minimal grade 3/4 toxicity and may be ideal for patients who are not suitable for platinum-based regimens
34、OModification of wTCF by substitution of cisplatin with oxaliplatin (E) and 5-FU with capecitabine (X) to generate wTEX may further improve activity and safety. This combination is worthy of further study医学课件64Key messagesKey messagesO Toxicity is more manageable with the modified TCF regimen Taxote
35、re-induced FN can be managed by either by adding G-CSF prophylaxis or by using a weekly regimen FN for TCF (q3w)=28% (TAX 325) FN for TCF (q3w) + G-CSF=12% (TAX 325) FN for wTCF=6%O A Taxotere/Eloxatin-based triplet regimen is already under investigation (GATE study)The results of this study confirm
36、 that Taxotere-based triplet therapy (wTCF) is superior to a Taxotere-based doublet (wTX) in the treatment of metastatic gastric carcinoma医学课件65 紫杉类药物是最有效的单药之一紫杉类药物是最有效的单药之一联合联合PDDPDD取得了实质性进展取得了实质性进展同时加入同时加入5-Fu5-Fu未见更好受益,反而增加未见更好受益,反而增加毒性毒性与放疗联合应用有良好的前景与放疗联合应用有良好的前景医学课件66食管癌:Irinotecan Irinotecan 化
37、疗 作作 者者 方方 案案 例例 数数有有 效效 率(率(%)Lin CPT 125/wk21 14EnzingerCPT 125/wk34 15BlankeCPT/5FU/LV32 22FindlayCPT/5FU/LV81 22Ilson CPT/PDD35 57AjaniCPT/PDD39 54PozzoCPT/PDD,Q3w72 28(MS 6.9 m.)CPT/5FU/wk74 34(MS 10.7 m.)GoldCPT/MMC17 65医学课件67MAGICMAGIC可切除胃癌可切除胃癌(74%)(74%)低位食管癌低位食管癌(14%)(14%)胃食管结合部胃食管结合部(11%)(
38、11%)ECF q213csECF q213csN=250N=253手术单纯手术ECF:E 50mg/m2C 60mg/m2FU 200mg/m2/d civCunningham D, et al. Perioperative Chemotherapy versus Surgery Alone for Resectable Gastroesophageal Cancer. N Engl J Med.2006;355(1):11-20.医学课件68MAGICMAGIC:无疾病进展生存率(PFSPFS)ECF+手术 vs.手术hazard ratio = 0.66;95% CI:0.53 to 0
39、.81; P0.001医学课件69MAGICMAGIC:总体生存率(OSOS)ECF+手术 vs.手术hazard ratio = 0.75; 95% CI:0.60 to 0.93; P = 0.009; 5-year survival rate:36% vs. 23%医学课件70MAGICMAGIC:肿瘤大小与术后分期ECF + SurgerySurgerySize3.1 cm5.0 cm (p = 0.001)T1 / T2T3 / T452%48%38%62% (p= 0.009)N 0/1N 2/384%16%76%24% (p = 0.01)医学课件71MAGIC MAGIC 结论
40、O对于可手术胃癌和低位食管腺癌患者,对于可手术胃癌和低位食管腺癌患者, ECF+ECF+手术与单纯手术相比手术与单纯手术相比: :缩小肿瘤大小缩小肿瘤大小降低术后分期降低术后分期显著提高显著提高PSFPSF显著提高显著提高OSOS医学课件72FFCD 9703FFCD 9703可切除胃癌可切除胃癌(89%)(89%)低位食管癌低位食管癌(11%)(11%)FP 2-3csFP 3-4csN=113N=111手术单纯手术FP:F 800mg/m2 d1-5P 100mg/m2 d1q28Final results of a randomized trial comparing preoperat
41、ive 5-fluorouracil (F)/cisplatin (P) to surgery alone in adenocarcinoma of stomach and lower esophagus (ASLE): FNLCC ACCORD07-FFCD 9703 trial.2007 ASCO Annual Meeting Abstract No: 4510 医学课件73FFCD 9703FFCD 9703结果SurgeryChemo + SurgerypN111113R073%84%0.043y DFS25%40%5y DFS21%34%0.003医学课件74MAGICMAGIC与F
42、FCD 9703FFCD 9703比较TrialNChemoHazard ratio for OSP5-year survival rate (%)MAGIC504ECF0.75 (0.60-0.93) 0.00936 versus 23FFCD 9703224FP0.69 (0.50-0.95)0.0238 versus 24以ECF或FP方案进行围手术期化疗可以显著延长可切除胃癌和低位食管腺癌患者的无进展生存期和总体生存期。医学课件75V325V325Phase III Study of Docetaxel and Cisplatin Plus Fluorouracil Compared
43、With Cisplatin and Fluorouracil As First-Line Therapy for Advanced Gastric Cancer: A Report of the V325 Study Group. J Clin Oncol, 2006, 24:4991-4997.未经治疗局部晚期未经治疗局部晚期或转移性胃癌患者或转移性胃癌患者Docetaxel 75 mg/m2 Cisplatin 75 mg/m2 d1 Fluorouracil 750 mg/m2/d (d1- 5) q3wN=227N=230Cisplatin 100 mg/m2 (d1) Fluoro
44、uracil 1,000 mg/m2/d (d1 - 5) q4wMedian follow-up is 13.6ms. 医学课件76DCFDCF与CFCF治疗效果比较Time to progressionOverall survival医学课件77DCFDCF与CFCF毒性比较医学课件78V325 V325 结论O对于未经治疗的晚期胃癌患者,对于未经治疗的晚期胃癌患者,DCFDCF的疾病进展的疾病进展时间、总体中位生存期均优于时间、总体中位生存期均优于CFCF。O20062006年年FDAFDA批准批准DCFDCF(多西他赛(多西他赛/ /顺铂顺铂/5-FU/5-FU)方案)方案用于治疗以前
45、未经化疗的晚期胃癌,包括胃食管用于治疗以前未经化疗的晚期胃癌,包括胃食管结合部癌。结合部癌。ODCFDCF方案的严重不良反应,尤其是方案的严重不良反应,尤其是3/43/4级粒细胞减级粒细胞减少,导致患者难以耐受少,导致患者难以耐受DCFDCF方案化疗。方案化疗。DCFDCF改良方改良方案(案(DCDC或或DFDF,紫杉醇替代多西紫杉醇)可减少不,紫杉醇替代多西紫杉醇)可减少不良反应,而疗效无差异。良反应,而疗效无差异。医学课件79+靶向治疗靶向治疗医学课件80 药物药物用法用法例数例数PR()()SDPD来源来源 Gefitinib500mg/d28263(12)1211Ferry.ASCO
46、2004 #4021 Gefitinib500mg/d28343(8)615Gneninge ASCO 2004 #4022二线二线(10例未评价)例未评价) Gefitinib250mg/d8w203(15)314Adelstein ASCO 2005 #4054Bevacizumab15mg/kg d1/3w 合并合并CPT.PDD1612(75)40Shah ASCO 2005 #4025 毒性:毒性:G腹泻、皮疹、呕吐;腹泻、皮疹、呕吐; B肺栓塞(肺栓塞(4)、血栓形成()、血栓形成(2)、胃穿孔()、胃穿孔(2)医学课件81 ErlotinibErlotinib食管癌病人食管癌病人
47、EGFREGFR超表达者超表达者30309090有有EGFREGFR超表达的病人预后差超表达的病人预后差以往单药疗效以往单药疗效 1212PRPR(ASCO 2004)ASCO 2004)2222例治疗结果例治疗结果 PR 9PR 9. SD 45.5. SD 45.5 PD 45.5PD 45.5. .(ASCO 2005)ASCO 2005)医学课件82医学课件83Fumikata H, Cancer Letters 226(2005) 37-47医学课件84医学课件85医学课件86医学课件87医学课件88医学课件89BevacizumabBevacizumabO贝伐单抗贝伐单抗(beva
48、cizumab(bevacizumab,Avastin)Avastin)为基因工程重为基因工程重组人源化抗组人源化抗VFGFVFGF单克隆抗体,主要通过抑制单克隆抗体,主要通过抑制VEGFVEGF发挥作用。发挥作用。O20042004年本品在美国获准上市,是第一种抗肿瘤血年本品在美国获准上市,是第一种抗肿瘤血管生成作用的抗癌新药,在转移性结肠、直肠癌管生成作用的抗癌新药,在转移性结肠、直肠癌中联合化疗作为一线药物。中联合化疗作为一线药物。医学课件90Bevacizumab+DCFBevacizumab+DCFO入选患者4747例晚期转移性胃癌和胃食管结合部癌患者。例晚期转移性胃癌和胃食管结合部
49、癌患者。O治疗方案bevacizumab 15 mg/kg d1, irinotecan 65 mg/m2 cisplatin 30 mg/m2 day1/8, q21d. Multicenter Phase II Study of Irinotecan, Cisplatin, and Bevacizumab in Patients With Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma. J Clin Oncol 2006, 24:5201-5206.医学课件91治疗效果(n=47)(n=47) Median T
50、TP= 8.3 ms (95% CI, 5.5 to 9.9 ms)Median OS=12.3 ms(95% CI, 11.3 to 17.2 ms)医学课件92可测量疾病与不可测量疾病疗效差异可测量 vs. 不可测量median survival 15.4 v 8.4mslog-rank P.04医学课件93常见毒性反应发生率医学课件94BEV+DCFBEV+DCF结论O贝伐单抗(抗贝伐单抗(抗VEGFVEGF抗体)联合伊立替康和顺铂对抗体)联合伊立替康和顺铂对晚期胃癌或食管胃结合部腺癌有效,进展期为晚期胃癌或食管胃结合部腺癌有效,进展期为8.38.3月,而中位生存期为月,而中位生存期为1