胃癌治疗现状及ASCO进展课件

1、Ohtsu et al 2003FP5-FUUFTMp valueNo. Patients10510570Response(%)34.8001PFS(weeks)0.001MS(weeks)NSUFTM, tegafur uracil / mitomycinWaters et al 1999ECFFAMTXp valueNo. pts137137Response46%21%0.00003FFS7.4 mo3.3 mo0.0001MST8.7 mo6.1 mo0.00052-yr SR14%5%0.03E Epirubicin 50 mg/

2、m2 ivC Cisplatin 60 mg/m2 ivF PVI 5-FU 200 mg/m2/dayq3wE Epirubicin 50 mg/m2 ivC Cisplatin 60 mg/m2 ivX Capecitabine 625 mg/m2/bid q3wE Epirubicin 50 mg/m2 ivO Oxaliplatin 130 mg/m2 ivF PVI 5-FU 200 mg/m2/dayq3wE Epirubicin 50 mg/m2 ivO Oxaliplatin 130 mg/m2 ivX Capecitabine 625 mg/m2/bid q3wPVI, po

3、rtal vein infusionCunningham D, et al. ASCO 2006 (Abstract LBA4017). Hazard ratio (95% CI): 0.86 (0.800.99)Time (years)Probability (%)01234560204060801008206178375212No. at risk48448028315-FU Capecitabine5-FU Capecita-bineCunningham D, et al. ASCO 2006 (Abstract LBA4017). Hazard ratio (95% CI): 0.92

4、 (0.801.10)Probability (%)012345602040608010010198187414810490474141CisplatinOxaliplatinCisplatinOxaliplatinTime (years)No. at riskCunningham D, et al. ASCO 2006 (Abstract LBA4017). 0130204060801002ECFEOXProbability (%)Time (years)Cunningham D, et al. ASCO 2006 (Abstract LBA4017). *p0.05 vs ECF; *p7

5、0 Adequate hematologic/biochemical parameters No prior palliative chemotherapyRANDOMISATIONTreatment until PD, consent withdrawn or unacceptable toxicity; tumor assessments q8wVan Cutsem E, et al. J Clin Oncol (accepted for publication).Log-rank p=0.0004Hazard ratio: 1.47 (95% CI: 1.191.83)Risk redu

6、ction: 32.1%00102030405060708090100DCFCF3691215182124Probability (%)Time (months)Van Cutsem E, et al. J Clin Oncol (accepted for publication).Log-rank p=0.0201Hazard ratio: 1.29 (95% CI: 1.041.61)Risk reduction: 22.7%03691215182124273033360102030405060708090100DCFCFTime (months)Van Cutsem E, et al.

7、J Clin Oncol (accepted for publication).Probability (%)DCFCF(n=221)(n=224)CR (%)21PD (%)1726ORRa (%)372595% CI30.343.4 19.931.7 p-value0.0195% CIResponders with responseduration 9 months (%)2614Response parameterSD (%)3031Median response duration (months)6.15.08.3 0.320.02aConfirmed and in

8、dependently reviewed Van Cutsem E, et al. J Clin Oncol (accepted for publication).0 3 6 9 12 15 18 21 24 27 100 90 80 70 60 50 40 30 20 10 0Time (months)Probability (%)DCFCFp=0.0088HR: 1.38 (95% CI: 1.081.76)Risk reduction: 27.5%aWorsening defined as a definitive decrease in PS by 1 KPS category vs

9、baselineMoiseyenko V, et al. WCGIC 2005 (Abstract O-013).Patients (%)DCF(n=221)CF(n=224)Lethargy1914Stomatitis2127Diarrhea19*8Infection137Nausea1417Vomiting1417Anorexia109Neurosensory8*31 event6959Adverse eventsaaPossibly or probably related to study treatment; treatment-emergent non-hematologic tox

10、icitiesoccurring at grade 3 to 4 in 5% of patients in either group*p 1050 (completed in March, 2007)FLAGS Trial(First-Line Advanced Gastric Cancer Study)RANDOMIZE-Type of disease(Locally advanced vsMetastatic 1 metastasis vs Metastatic 1 metastases) - Prior adjuvant CT- Measurable disease - CentersC

11、isplatin 75 mg/m2 IV Day 1S-1 25mg/m2 bid po Day 1-21Cycles repeated every 4 weeksCisplatin 100 mg/m2 IV Day 1Cycles repeated every 4 weeks5-FU 1000 mg/m2/day CIV Day 1-5 (over 120 hours ) RANDOMISATIONARM A Taxotere 40 mg/m2 D1 S-1 80 mg/m2 D1-14 q 3 weeksARM B S-1 80 mg/m2 D1-28 q 6 weeksUNTILPDST

12、ART Trial(S-1 and Taxotere for Advanced Gastric Cancer Randomized Phase III Trial) Collaborative Japan-Korea Trial Patient accrual: 628 Primary endpoint: Overall survival Center Measurable ds (by RECIST)K. Ridwelski 2008ASCO #4512 N=270Patients withadvanced gastricand gastrooesophagealjunctionadenoc

13、arcinomaRTEDocetaxel 75 mg/m2 +Oxaliplatin 130 mg/m2 q 3 wkTEFDocetaxel 50 mg/m2 +Oxaliplatin 85 mg/m2 +folinic acid 400 mg/m2 +5-FU 2400 mg/m2/46h (no bolus), q 2 wkTEXDocetaxel 50 mg/m2 +Oxaliplatin 100 mg/m2 q 3 wk +Capecitabine 625 mg/m2 bid continuouslyMedian TTP: 5.4 months Overall survival :

14、12.3 months ORR 41.0%, SD 21.6%30.0025.0020.0015.0010.005.000.00TTP(m onth)TTP(m onth)1.00.20.0C um P robabi l i t y of S urvi valC um P robabi l i t y of S urvi valCensoredSurvi val Functi onSurvival FunctionSurvival Function30.0025.0020.0015.0010.005.000.00O S(m onth)O S(m onth)1.00.80.60

15、.40.20.0C um propot i on % S urvi valC um propot i on % S urvi valCensoredSurvi val Functi onSurvival FunctionSurvival Function5.4 months (95% CI, 2.4-8.4 months) 12.1 months (95% CI, 10.0-14.2months) TTPOSPhase II Clinical Trail of XELOX as first line treatment in patients with unresectable or meta

16、static gastric cancer 疾病控制率为疾病控制率为 76%（ITT）TTP and OS of eligible patients receiving XELOX) 中位中位OS 11.1 months (95% CI, 5.6-16.5 months)中位中位TTP 5.8 months (95% CI, 3.4 to 8.2 monthsTCX for AGC (1st line): Phase I / II studyChemotherapy (every 3 weeks)Docetaxel 60 mg/m2 iv D1Xeloda 937.5 mg/m2 po bid D1-14Cisplatin 60 mg/m2 iv D1Efficacy (N = 40)Response: 4 CRs, 23 PRs: 68% 10 Op: 4 pathologic CRsTTP: 7.8 mo, OS: 16.9 moToxicityG3/4 neutropenia 63%, neutropenic fever 10%, 1 deathG3 asthenia 38%, G3 HFS 2.5%, G3 diarrhea 2.5%Kang YK, et al. Proc ASCO 2004At: . Accessed November 9, 200