1 / 35

What is the reference cytotoxic regimen in advanced gastric cancer?

What is the reference cytotoxic regimen in advanced gastric cancer?. Florian Lordick Klinikum Braunschweig Germany. Chemotherapy in Advanced Gastric Cancer – What do we know ? (I). Chemotherapy prolongs survival Chemotherapy improves symptom control

alissa
Download Presentation

What is the reference cytotoxic regimen in advanced gastric cancer?

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. What is the reference cytotoxic regimen in advanced gastric cancer? Florian Lordick Klinikum BraunschweigGermany

  2. Chemotherapyin AdvancedGastricCancer– What do weknow? (I) • Chemotherapyprolongssurvival • Chemotherapyimprovessymptomcontrol • Combinationsaremoreactivethanmonotherapy Wagner et al. J ClinOncol2006; 24: 2903-9 • Elderly(>70 yearsage) benefitequally Trumper et al. Eur J Cancer 2006; 42: 827-34 Establishedstandard:Platinum-fluoropyrimidine-combination

  3. Chemotherapyin AdvancedGastricCancer– What do weknow? (I) • Oxaliplatincansubstituteforcisplatin • Oral fluoropyrimidinescansubstitutefor i.v. 5-FU • A 3rd drugmakesCTxmoreeffective but moretoxic Al-Batran et al. J Clin Oncol 2008; 26: 1435-1442 Cunningham et al. N Engl J Med 2008; 358: 36-46 Kang et al. Ann Oncol 2009; 20: 666-673 Cunningham et al. N Engl J Med 2008; 358: 36-46 Ajani J et al. J ClinOncol2010; 28: 1547-1553 Van Cutsem et al. J ClinOncol2006; 24: 4991-7Wagner et al. J ClinOncol2006; 24: 2903-9

  4. Oxaliplatin

  5. Oxaliplatinin GastricCancer Real-2-Study (UK) E EpirubicinC CisplatinF Fluorouracil R A N D O M E EpirubicinC CisplatinX Xeloda (Capecitabine) N=964 E EpirubicinO OxaliplatinF Fluorouracil E EpirubicinO OxaliplatinX Xeloda (Capecitabine) Cunningham D et al. N Engl J Med 2008;358:36-46

  6. Oxaliplatinin GastricCancer Real-2-Study Cunningham D et al. N Engl J Med 2008;358:36-46

  7. Oxaliplatinin GastricCancer AIO-Study (Germany) R A N D O M PCisplatinLLeucovorinF 5-Fluorouracil N=220 OOxaliplatinL LeucovorinF 5-Fluorouracil Al-Batran SE et al. J Clin Oncol 2008;26:1435-1442

  8. AIO-study: FLO versus FLP Overall population PFS: p = 0.077 OS: p = 0.506 Al-Batran SE et al. J Clin Oncol 2008;26:1435-1442

  9. AIO-study: FLO versus FLP Elderly (patients> 65 years) PFS: p = 0.029 OS: p = n. s. Al-Batran SE et al. J Clin Oncol 2008;26:1435-1442

  10. Oxaliplatincansubstituteforcisplatin in gastriccancer!Potential advantages intheelderlyandfrailpopulation

  11. Oral fluoropyrimidines

  12. Capecitabine in GastricCancer Real-2-Study (UK) E EpirubicinC CisplatinF Fluorouracil R A N D O M E EpirubicinC CisplatinX Xeloda (Capecitabine) N=964 E EpirubicinO OxaliplatinF Fluorouracil E EpirubicinO OxaliplatinX Xeloda (Capecitabine) Cunningham D et al. N Engl J Med 2008;358:36-46

  13. Capecitabine in GastricCancer Real-2-Study Cunningham D et al. N Engl J Med 2008;358:36-46

  14. Capecitabine in GastricCancer ML17032-Study (Korea) R A N D O M F 5-FluorouracilPCisplatin Primary endpoint: overallsurvival(non-inferiority) N=316 X Xeloda (Capecitabine)PCisplatin Kang YK et al. Ann Oncol 2009; 20: 666-673

  15. ML17032-Study: XP versus FP Response rate 46% vs. 32%p=0.02 Progression-freesurvival 5.6 vs. 5.0 monp<0.001(non-inferior) Survival 10.5 vs. 9.3monp=0.008 (non-inferior) Kang YK et al. Ann Oncol 2009; 20: 666-673

  16. S-1/cisplatinversus 5-FU/cisplatin FLAGS-Study (multinational Western World) R A N D O M S-1 25mg/m22x/d d1-21 Cisplatin 75mg/m2 d1 q4w Primary endpoint: overallsurvival(superiority) N=1053 5-FU 1000mg/m2 d1-5 Cisplatin 100mg/m2 d1 q4w Ajani J et al. J ClinOncol2010; 28: 1547-1553

  17. S-1/cisplatinversus 5-FU/cisplatin In a Non-Asian patientpopulation S-1 was not superiorto 5-FU Ajani J et al. J ClinOncol2010; 28: 1547-1553

  18. S-1/cisplatinversus 5-FU/cisplatin Toxicity in favorof S-1/cisplatin Ajani J et al. J ClinOncol2010; 28: 1547-1553

  19. Oral fluoropyrimidinescansubstitutefor i.v. 5-FU in gastriccancer!Lessseveretoxicityfor S-1/cisplatin

  20. Doubletsortriplets?Andwhichisthe relevant thirddrug?

  21. Cisplatinum HR = 0.83 (95% CI 0,76 – 0,91) in favorofcisplatinum Wagner et al. J ClinOncol2006; 24: 2903-9

  22. Anthracyclines HR = 0.77 (95% CI 0,62 – 0,95) in favorofanthracyclines Wagner et al. J ClinOncol2006; 24: 2903-9

  23. AnthracyclinesECF versus EOX Real-2-Study (UK) HR = 0.80 (95% CI, 0.66 to 0.97; P=0.02) Cunningham D et al. N Engl J Med 2008;358:36-46

  24. Docetaxel Tax-325-Study (multinational) Docetaxel 75mg/m2 d1 Cisplatin 75mg/m2 d1 5-FU 750mg/m2 d1-5 q3w R A N D O M Stage IVn=445 Primary endpoint: time toprogression (TTP) Cisplatin 100mg/m2 d1 5-FU 1000mg/m2 d1-5 q4w Van Cutsem et al. J Clin Oncol2006; 24: 4991-7

  25. Docetaxelas 3rd DrugTAX-325 Response rate 37% vs. 25% p=0.01 Time toprogression 5.6 vs. 3.7 months p<0.01 Survival 9.2 vs. 8.6 months p=0.02 Kaplan-Meier curve: time toprogression Van Cutsem et al. J Clin Oncol2006; 24: 4991-7

  26. DCF Toxicity Hematologictoxicityin DCF Neutropenia grade 3/482% Febrile neutropenia30% Van Cutsem et al. J Clin Oncol2006; 24: 4991-7

  27. Alternative docetaxel-basedregimen(AIO studies) GastroTax-1 regimenDocetaxel 40mg/m2 + cisplatin40mg/m22-weekly 5-FU 2000mg/m2 – folinicacid 200mg/m2weeklyResponse rate 46.6%Time toprogression (metastatic) 8.1 monthsSurvival (metastatic) 15.1 months Lorenzen et al. Ann Oncol2007; 18: 1673-9 FLOT regimenDocetaxel 50mg/m2 + modified FOLFOX 2-weeklyResponse rate 53% Time toprogression5.3 months Survival11.3 months Al-Batran et al. Ann Oncol 2008; 19:1882-87

  28. Alternative docetaxel-basedregimen(MSKCC) ModifiedDCF vs. classic DCF + G-CSF (rand. Ph. II) Median follow up 10.3 mo Modified DCF Classic DCF Fraction Surviving 12.6 mo 15.1 mo Months Shah et al. ASO 2010; abstract 4014

  29. The futureoftriplets in gastriccancer:Sequentialtreatment? AIO – YMO – Maintain Study (proposal) Induction 6 cyclesFLOT(3 months) Arm A (120 pat.) De-escalationS-1 CR, PR, SD R 2:1 Arm B (80 pat.) FLOT Progression

  30. Triplets aremoreeffectivethandoublets!But…Side effectsare an issue!Patients‘ preferences matter!Watch out foroverlappingsideeffectsandinteractions, whencombiningwithbiologics

  31. Arm A: EOX R Arm B: EOX-Panitumumab 3 + 1 = X…whentheunpredictablecomestrue REAL-3 study • EOX (Arm A): • Epirubicin 50mg/m2 IV D1 • Oxaliplatin 130mg/m2 IV D1 • Capecitabine 1250mg/m2/day PO in two divided doses D1-21 • mEOX-P (Arm B)1: • Epirubicin 50mg/m2 IV D1 • Oxaliplatin 100mg/m2 IV D1 • Capecitabine 1000mg/m2/day PO in two divided doses D1-21 • Panitumumab 9mg/kg IV D1 Wardell et al. ASO 2012; abstractLBA 4000

  32. 3 + 1 = X…whentheunpredictablecomestrue 100 80 60 Probability of Survival (%) 40 EOX HR 1.37 (95% CI: 1.07 – 1.76) 20 EOX-P 0 6 18 30 0 12 24 36 Months from Randomisation Number at risk EOC 275 49 3 EOC-P 278 38 2 Wardell et al. ASO 2012; abstractLBA 4000

  33. Reference regimensforadvancedgastriccancer in 2012 Triplets Indication: Severetumorsymptoms Patient preference (mostactivetx) Intactorganfunctions Regimens: EOX (epirubicine, oxaliplatin, cape.) mod. DCF (docetaxel, cisplatin, 5FU) FLOT (docetaxel + mod. FOLFOX)

  34. Reference regimensforadvancedgastriccancer in 2012 Doublets Indication: Patient preferenceforlesstoxicity Impairedorganfunctions Combinationwithbiologics Regimens: Capecitebine-cisplatin S-1-cisplatin FOLFOX-like / CapOx (elderly)

  35. Doubletor Triplet? 2 : 0 or 3 : 0 Let‘swinthematch!

More Related