《胃癌化学治疗暨分子标靶治疗的最新进展》由会员分享，可在线阅读，更多相关《胃癌化学治疗暨分子标靶治疗的最新进展（54页珍藏版）》请在金锄头文库上搜索。
1、胃癌化学治疗暨分子标靶治疗药物胃癌化学治疗暨分子标靶治疗药物胃癌化学治疗暨分子标靶治疗药物胃癌化学治疗暨分子标靶治疗药物 的最新进展的最新进展的最新进展的最新进展 Recent Progress in Drug Treatment for Advanced Gastric Cancer from chemotherapy to molecularly targeted therapy叶 坤 辉叶 坤 辉 Kun-Huei Yeh, M.D., Ph.D.台湾大学医学院附属医院 肿瘤医学部台湾大学医学院 临床医学研究所台湾大学医学院附属医院 肿瘤医学部台湾大学医学院 临床医学研究所Gastric
2、 cancer1. Parkin D et al. CA Cancer J Clin 2005; 55: 74-108 2. Ahn Y-O. Jpn J Clin Oncol 2002; 32(Suppl. 1): S32-S36Incidence per 100,000MalesFemalesChina141.419.2Taiwan 20.012.0Japan162.126.1Korea271.134.9Eastern Europe129.612.8South America124.212.2Central America115.210.8North America17.43.4Gastr
3、ic Cancer in TaiwanIncidenceMortalityNew cases /YearRate (/100,000)No. /YearRate (/100,000)Total 358015.9239810.5Male228820157113.6Female1292128277.4The No. 5 cancer killer in TaiwanLocalized Disease30-53 %27 %Op. mortality0.8-2 %3.6-10 %5-Year Survival40-60 %20%Chemotherapy Ethnic differences Regul
4、atory differences Cultural differencesBiology (Cardia) Weekly DIYeh KH et al, ASCO 2006: A14063Repeat cycle at day 29 (Q 4 wks)Efficacy 29- 74%, 95% C.I.) 0 of the 6 patients with prior exposure to HDFL +/- cisplatin responded (R.R.= 0%) (p value = 0.054 by Fishers exact test)The median time to prog
5、ression and overall survival of the intent-to-treat group was 6 and 10 months, respectively. Yeh KH et al, Oncology 2005; 69: 88-95.Paclitaxel-HDFLR A N D O M I Z EDocetaxel 75 mg/m2IV over 1 hr, D1 Cisplatin 75 mg/m2IV over 1- 3 hrs, D1 5-FU 750 mg/m2/day by CIV over 5 daysQ3W227 patientsCisplatin
6、100 mg/m2IV over 1-3 hrs, D1 5-FU 1000 mg/m2/day by CIV over 5 daysQ4W230 patients Measurable or evaluable metastatic or measurable locally recurrent gastric adenocarcinoma Age 18 years old KPS 70 Adequate hematological and biochemical parameters Signed written informed consentStratification factors
7、:Liver involvement (y/n) Prior gastrectomy (y/n) Measurable vs evaluable disease Weight loss (5% vs 5%) in prior 3 months CenterTumor assessments planned every 8 weeks in both armsPhase III Study Design (TAX 325)Treatment until PD, consent withdrawn or unacceptable toxicityVan Cutsem et al. J Clin O
8、ncol 2006; 24: 4991Randomized Phase III Trial in Advanced Gastric Cancer (TAX 325)DCFDCF 111 43% 38.7% 5.2 m 10.2 m 84% 20% 23%CF 112 41% 23.2% 3.7 m 8.5 m 60% 8% 30%Case No. Liver mets + RR Median TTP Median OS Gr 3-4 neutropenia Gr 3-4 diarrhea Gr 3-4 stomatitisCF: 5-FU 1000 mg/m2/d D1-5 + cisplat
9、in 100 mg/m2, D1 DCF: docetaxel 75 mg/m2D1 + 75% dose of 5-FU/cisplatin in CFp0.012 0.0008 0.0064Van Cutsem et al. JCO 2006.RestOxaliplatin plus HDFL in Advanced Gastric Cancer: 1st-lineOxaliplatin 65 mg/m2, 2-hour i.v. infusionDay 18HDFL 5-FU2,600 mg/m2+ leucovorin 300 mg/m2, 24-hour i.v. infusion
10、repeat cycle at day 22 (Q 3 wks)Design: phase II, primary end-point: response rates Follow-up CT scan and PES, every 2 cycles (+ response documentation)Oxaliplatin-HDFLChao Y, Yeh KH, et al. Br J Cancer 2004; 91: 453-458. Efficacy 91: 453-458. REAL 2 (2 x 2 randomization)EEpirubicin 50 mg/m2 iv CCis
11、platin 60 mg/m2iv FPVI 5-FU 200 mg/m2/d*EEpirubicin 50 mg/m2 iv CCisplatin 60 mg/m2iv XCapecitabine 625 mg/m2/bdEEpirubicin 50 mg/m2 iv OOxaliplatin 130 mg/m2iv FPVI 5-FU 200 mg/m2/d*EEpirubicin 50 mg/m2 iv OOxaliplatin 130 mg/m2iv XCapecitabine 625 mg/m2/bdPlanned treatment duration 24 weeks (8 cyc
12、les) CT scan baseline, 12 weeks and 24 weeks* PVI 5FU delivered by central venous access catheterAll given every 3 weeksCunningham D, et al. N Engl J Med 2008; 358:36-46.Best overall Response24.7%15.2%0.69442.4% (36.1-48.8)39.8%2.6%231EOF n=23528.0%31.3%40.7% (34.5-46.8)36.6%4.1%246ECF n=249234237Ev
13、aluable24.4%21.5%PD or died27.8%32.1SD0.1120.202p-value vs ECF47.9% (41.5-54.3)46.4% (40.0-52.8)CR + PR 95% CI44.0%42.2%PR3.9%4.2%CREOX n=239ECX n=241Response (%)Cunningham D, et al. N Engl J Med 2008; 358:36-46.Oxaliplatin is not inferior to Cisplatin for Advanced Gastric CancerThe REAL-2 study sho
14、ws that Oxaliplatin-containing chemotherapy is associated with manageable toxicity more favorable safety profile than cisplatin-based regimens Oxaliplatin is not inferior to cisplatin (primary objective) EOX is associated with improved efficacy vs ECF median OS 11.2 vs 9.9 months; p= 0.02EOX, epirub
15、icin-oxaliplatin-capecitabine; ECF, epirubicin-cisplatin-5-FUXP (n=160) Cisplatin 80 mg/m2on Day 1 Capecitabine 1000 mg/m2bid on Days 114, every 3 weeks x 5FP (n=156) Cisplatin 80 mg/m2on Day 1 5-FU 800 mg/m2/day on Days 15, every 3 weeks x 5316 patients with previously untreated, measurable, metast
16、atic gastric adenocarcinomaaR RXP versus FP in Advanced Gastric Cancer: Phase III study (non-inferiority)Kang YK, et al. ASCO 2006 (Abstract LBA4018).aMedian age 56 years; median Karnofsky PS 80; similar male/female balance Primary endpoint: PFS (non-inferiority)1916NeutropeniaGrade 34 toxicity, %0.0302941ORR, %97Vomiting1.5 m2, respectively, on days 1 - 28 every 42 days/cycle.Number of pts, n34 (29: evaluable
