胃治疗现状及ASCO进展

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adequate hematologic/biochemical parameters no prior palliative chemotherapyrandomisationtreatment until pd, consent withdrawn or unacceptable toxicity; tumor assessments q8wvan cutsem e, et al.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 cfthe tcf regimen is the proof of the concept that docetaxel provides the benefit our patients needdocetaxel should be incorporated in safer regimen using oxaliplatin, s-1 or capecitabinedevelop a regimen to allow addition of a bio

11、logicn=170cpt-11 80mg/m2cf 500mg/m25fu 2000mg/m2 civ1/w x 6w n=163cddp 100mg/m2 d15fu 1000mg/m2/d d1-5q4wn=333 agcrr ttp 5.0m 4.2m (p=0.088)ttf 4.0m 3.4m (p=0.002)os 9.0m 8.7m p0.53m. dank 2005 asco abs 4003dank, et al. asco 2005hematologic g3/4neutropenianeutropenic fevernonhematologic g3/4anydiarr

12、heavomitingstomatitisrenalfofiri25%5%40%22%7%2%0.6%pf52%10%44%7%8%17%6%- center- ps- unresectable vs recurent, adj crx vs recurrent, no adj crxrandomisationarm a (control)5-fu civ 800 mg/m2 d1-5 q 4 weeksarm bs-1 80 mg/m2 d1 - 28 q 6 weeksuntilpd primary endpoint: overall survival a vs b: non-inferi

13、ority, a vs c: superiorityarm ccpt-11 70 mg/m2 d1,15 cddp 80 mg/m2 d1 q 4 weeksboku n, et al. proc am soc clin oncol 2007 (#4513) boku n, et al. proc am soc clin oncol 2007 (#4513) randomisationarm a s-1 40-60 mg bid for 28 d q 6 weeksarm b cisplatin 60 mg/m2 on d8 s-1 40-60mg bid for 21 d q 5 weeks

14、untilpd primary endpoint: overall survival (superiority) center ps unresectable vs. recurrentnarahara h et al. asco 2007narahara 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 t

15、rial(first-line advanced gastric cancer study)randomize-type of disease(locally advanced vsmetastatic 1 metastasis vs metastatic 1 metastases) - prior adjuvant ct- measurable disease - centerscisplatin 75 mg/m2 iv day 1s-1 25mg/m2 bid po day 1-21cycles repeated every 4 weekscisplatin 100 mg/m2 iv da

16、y 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 weeksuntilpdstart trial(s-1 and taxotere for advanced gastric cancer randomized phase iii trial) collaborative japan-kore

17、a trial patient accrual: 628 primary endpoint: overall survival center measurable ds (by recist)k. ridwelski 2008asco #4512 meta-analysis of chemotherapy inadvanced gastric cancerall randomized trials closed to accrual by end of 2004 eligibletrials with neoadjuvant or adjuvant treatment excludedendp

18、oint: osmeta-analysis of chemotherapy inadvanced gastric cancercisplatin versus no cisplatin 7 rcts, n=1677, hr=0.98, p=0.59irinotecan versus no irinotecan 3 rcts, n=550, hr=0.89, p=0.36anthracycline versus no anthracycline 7 rcts, n=1501 pts, hr=0.94, 95%ci=0.84-1.06, p=0.31taxane versus no taxane

19、3 rcts, n=572, hr=0.82, 95%ci=0.68-0.99, p=0.03gate phase ii trial of first-line docetaxel oxaliplatin in advanced gastric cancern=270patients withadvanced gastricand gastrooesophagealjunctionadenocarcinomartedocetaxel 75 mg/m2 +oxaliplatin 130 mg/m2 q 3 wktefdocetaxel 50 mg/m2 +oxaliplatin 85 mg/m2

20、 +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 : 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

21、.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)1.00.20.0c um propot i on % s urvi valc um propot i on % s urvi valcensoredsurvi val functi onsurvival

22、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 metastatic 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.

23、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, 2006.metastatic esophagogastric canceririnotecan +