1 Kolon Kanserinde Adjuvan Tedavi Prof. Dr. N. Faruk AYKANTOD KursuGaziantep24 Ekim 2003
2 Prognosis by Stage Stage TNM Dukes 5-yr survival I T1 N0 M0 A >90% 85%IIT3/4 N0 M0B2/370-80%IIIT2 N1/2 M0T3 N1/2 M0T4 N1 M0C1C2C325-60%IVAny T/N M1D5-30%ESMO Guidelines 2001
3 Kolon Kanserinde Tedavi Primer Tedavi : Cerrahi Rezeksiyon(Hastaların % 50’si kürabl)NCI-PDQ Statement March 2002
4 Kanser Tedavisinde Kanıt Düzeyleri (NCI-2002) Çalışma DizaynıHedefRandomize, kontrollü klinik çalışmalar, metaanalizlerÇift körŞemaya göreRandomize olmayan klinik çalışmalarOlgu sunumlarıPopülasyon, ardışık seriArdışık seriArdışık olmayan olgularTotal mortalite (GSK)Nedene özgül mortaliteYaşam kalitesiDolaylı verilerHastalıksız sağkalımProgresyonsuz sağkalımTümör cevap oranıSource: US NCI / Cancer information PDQ
5 Level Of Evidence: How Is It Recorded? DESIGNEND POINTSExample 1Randomized, controlled (1)Non-blinded (ii)Overall survival (A)1iiAExample 2Non-randomized (2)Non-blinded (ii)Disease-free survival (Di)2iiDiMAY BE USED FOR PRIMARY AND SECONDARY ENDPOINTS
7 Kolon Ca – Adjuvan KT Evre III (Dukes’ C) 5-FU/LEV FU/FA(12 ay) (6 ay)?NIH ASCO
8 Kolon Ca – Adjuvan KT Evre III (Dukes’ C) Cerrahi FU/Lev (12 ay) > Cerrahi (1iiA)(n:304) (n:315)NCCTG 1989, INT – 1995Toplam vaka sayısı: 9295 yıl HSK: % 45 vs % 63 p<0.00015 yıl GSK: % 54 vs % 65 p<0.007Moertel CG et al: Ann Intern Med 122: , 1995
10 Kolon Ca – Adjuvan KT Evre III (Dukes’ C) Cerrahi FU/FA (6 ay) > Cerrahi (1iiA)n: n:151IMPACT 1995, INTToplam vaka sayısı: 3095 yıl HSK: % 58 vs % 74 p<0.0045 yıl GSK: % 63 vs % 74 p<0.01O’Connell et al: J Clin Oncol, 15: , 1997
11 Kolon Ca – Adjuvan KT Evre III (Dukes’ C) Cerrahi 5-FU/FA (6 ay) = Cerrahi FU/Lev (12 ay)(1iiA) n: ? n: ?INT ve 1998Toplam vaka sayısı: 37595 yıl HSK: % 59 vs % 56 p:0.095 yıl GSK: % 66 vs % 63 p:0.09(5-FU/FA/Lev 6 ay FU/FA’dan üstün değil !)Haller DG et al: Pro ASCO, 17:256a, 1998 (abstr.982)
12 Kolon Ca – Adjuvan KT Standart KT rejimleri (ASCO 1997) Mayo rejimi
13 Kolon Ca – Adjuvan KT Standart KT rejimleri Dublin - 2001
14 Adjuvant Chemotherapy For Stage III Colon Cancer The oxaliplatin MOSAIC trial of LV5FU2 vs. FOLFOX4 recruited 1123 pts/arm40% stage II patients3-year DFS results were presented at ASCO 2003:MOSAIC 3-year DFSOverallStage IIStage IIILV5FU272.9%83.9%65.5%FOLFOX477.8%86.6%71.8%P-valueP<.01HR=.77-HR=.82HR=0.76De Gramont A, et al: Pro ASCO, abstr.1015, 2003
16 Irinotecan Adjuvant Clinical Development Programme: Main Trials In Stage III Colon Cancer RegimenPtsEndpointsACCORD 2CPT-11+LV5FU2LV5FU24003-yr DFSSafetyOverall survivalPETACC-3(V-307)CPT-11+ inf 5-FU/FA(LV5FU2 or AIO)Inf 5-FU/FA2333Translational resQUASAR IICPT-11+ capecitabineBolus 5-FU/FA3450
18 Irinotecan/5-FU/FA Adjuvan KT’de PETACC-3 çalışmasıCPT-11/5-FU/FA*5-FU/FA**: De Gramont, AIO şeması
19 PETACC-3 (V-307) Group A1 (AIO, every wk) 2 hours CPT-11 Folinic acid500 mg/m²2 hours5-FU IV 2000 mg/m2 24 hours CPT-1180 mg/m260minGroup A2 (LV5FU2, every 2 wks)Folinic acid200 mg/m²5-FU bolus400 mg/m22 hours5-FU IV 600 mg/m2 22 hoursD1 & D2D1 CPT-11180 mg/m260min
20 Xeloda® as adjuvant treatment for colon cancer: X-ACT study Open-label, randomised, multicentre, phase III trialRecruitment of 1,956 Dukes’ C colon cancer patients is on target for completion in 2001Xeloda 1,250mg/m2 twice daily, days 1–14 every 21 days x 8 versus 4-weekly Mayo Clinic regimen x 6Disease-free survival as 1° endpoint2° endpoints: overall survival, safety, quality of life, health economics, measurement of biochemical markers in selected centres19. Xeloda® as adjuvant treatment for colon cancer: X-ACT studyA phase III trial, the Xeloda Adjuvant Chemotherapy Trial (X-ACT), is evaluating Xeloda as adjuvant treatment for Dukes’ C colon cancer. This large, global trial is being conducted in 27 countries with the recruitment of 1,956 patients undergoing surgery for colon cancer and is on target for completion in Patients are randomised to receive either eight cycles of intermittent Xeloda 1,250mg/m2 twice daily for 14 days followed by a 7-day rest period or six cycles of 4-weekly Mayo Clinic regimen.The primary objective of the trial is to demonstrate at least equivalent disease-free survival with Xeloda compared with Mayo Clinic regimen. In addition, overall survival, safety, QoL and health economics will be assessed. The activity of the biochemical markers thymidine phosphorylase, dihydropyrimidine dehydrogenase (DPD) and thymidylate synthase will be measured in tumour tissue samples collected during surgery at selected centres and these will be evaluated in relation to treatment outcome.
22 Kolon Ca – Adjuvan KT Evre II (Dukes’ B) Cerrahi FU/FA (6 ay) ≥ Cerrahi (1iiDi) % 2 HSK avantajı; NSABP ve Meta-analiz 1999Riskli sub-gruplar;PerforasyonTam ObstrüksiyonAnöploidiYüksek S-faz fraksiyonu18q delesyonuMSSKontrollü klinik çalışma !
23 Irinotecan Adjuvant Clinical Development Programme: Other Studies CALGB C89803Irinotecan + bolus 5-FU/FA weekly vs bolus 5-FU/FA weekly1263 patients, includes stage II + III and PS-2 patients3-yr DFS, safety, overall survival, translational researchAEROIrinotecan + LV5FU2 vs 5-FU/FA (Mayo Clinic or LV5FU2)600 patients with stage II and III rectal cancer5-yr DFS, safety, overall survivalPETACC-4Irinotecan + 5-FU/FA (TTD, LV5FU2, AIO) vs 5-FU/FA1976 patients with stage II colon cancer5-yr DFS, safety, overall survival, translational research
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