1 / 22

C. Rödel, H. Becker, R. Fietkau , U. Graeven ,

Preoperative chemoradiotherapy and postoperative chemotherapy with 5-FU and oxaliplatin versus 5-FU alone in locally advanced rectal cancer : First results of CAO/ARO/AIO-04. C. Rödel, H. Becker, R. Fietkau , U. Graeven ,

ura
Download Presentation

C. Rödel, H. Becker, R. Fietkau , U. Graeven ,

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. Preoperativechemoradiotherapyand postoperative chemotherapywith 5-FU andoxaliplatin versus 5-FU alone in locallyadvancedrectalcancer: First resultsof CAO/ARO/AIO-04 C. Rödel, H. Becker, R. Fietkau, U. Graeven, W. Hohenberger, C. Hess, T. Hothorn, M. Lang-Welzenbach, T. Liersch, L. Staib, C. Wittekind, R. Sauer German RectalCancer Study Group

  2. 5-FU: 500 mg/m²/d 5-FU: 1 g/m2/d x 5 RT: 50.4 Gy+5.4 Gy R 5-FU: 1 g/m2/d x 5 5-FU: 500 mg/m²/d TME TME RT: 50.4 Gy Background (1): CAO/ARO/AIO-94 Sauer R. et al., N Engl J Med 2004:351:1731-40

  3. 0.3 0.5 p = 0.006 0.4 38% 0.2 0.3 Postop CRT Distant Metastases Local Failure 36% 13% 0.2 Postop CRT 0.1 6% Preop CRT 0.1 Preop CRT 0.0 0.0 0 60 12 24 36 48 0 60 12 24 36 48 Months Months Background (2): CAO/ARO/AIO-94 More effectivesystemic therapyneeded!

  4. Background (3): Phase I/II Trials D1 D8 D22 D29 Ox Cap D1 D22 T M E RT x4 … Ox: 130 mg/m²/dCap: 2000 mg/m²/d Ox: 50 mg/m²/dCap: 1650 mg/m²/dRT: 1.8 Gy to 50.4 Gy Rödel C. et al., J ClinOncol 2003;21:3098-104 Rödel C. et al., J ClinOncol 2007;25:110-117

  5. Phase III: CAO/ARO/AIO-04 Best arm of CAO/ARO/AIO-94: T M E RT 50.4 Gy + 5-FU1000 mg/m² days 1-5 + 29-33 5-FU500 mg/m² d 1-5, q29 4 cycles (4 months) Based on phase I/II trials: RT 50.4 Gy + 5-FU/OXOx: 50 mg/m² d 1, 8, 22, 29 5-FU: 250 mg/m² d 1-14 + 22-35 Note:Chemogap 3rd weekof RT ! mFOLFOX6Oxaliplatin: 100 mg/m² d1,q15 FolinicAcid:400 mg/m² d15-FU: 2400 mg/m² d1-28 cycles (4 months)

  6. Main InclusionCriteria • Carcinomaofrectum • Within 12 cm above anal verge • ECOG PS 0-2 • cT3/4 and/orcN+, cM0 • Staging: EUS+CT and/or MRI

  7. Study Endpoints • Primary: Disease-freesurvival • - 3y-DFS: 75% to 82% • - 80% power, alphaerror: 0.05 • - Sample size: 1200 patients • Main Secondary: • - Toxicity and compliance • - R0 resection rate • - pCR rate and Tumor Regression (TRG)

  8. CONSORT 7/2006 – 2/2010: 1265 patientsrandomized Arm 5-FU n=637 Arm 5-FU/Ox n= 628 Eligible n= 624 Eligible n= 613 Preop CRT n= 621 (99%) Preop CRT n= 607 (99%) Surgery n= 603 (97%) Surgery n= 586 (97%) StartedadjCTx n= 460 (74%) StartedadjCTx n= 445 (73%)

  9. CONSORT 7/2006 – 2/2010: 1265 patientsrandomized Arm 5-FU n=637 Arm 5-FU/Ox n= 628 Tox/Compliance Surgery/Pathology Intention- to-treat Eligible n= 624 Eligible n= 613 Preop CRT n= 621 (99%) Preop CRT n= 607 (99%) Surgery n= 603 (97%) Surgery n= 586 (97%) StartedadjCTx n= 460 (74%) StartedadjCTx n= 445 (73%)

  10. *Strata; Stagedby EUS / CT / MRI in 85%, 73%, 49%, respectively

  11. TME good TME moderate TME poor ventral view dorsal view peritoneal fold distal resectionmargin

  12. *accordingtoDworak et al.; Int J Colorectal Dis 1997;12-19-23

  13. *p= 0.045 (unplanned, exploratory)

  14. Compliance AdjuvantChemotherapy noadj. therapy received missing 100% 90% 80% 70% 5 F U 60% m FOLFOX 6 Percentotpatientsbycycle 50% 40% 30% 20% 10% 0% Adj 3 Adj2 Adj 4 Adj1 Cycle 3/4 Cycle 1/2 Cycle 5/6 Cycle 7/8

  15. 1Aschele et al., J ClinOncol 2009;27:170s abstr CRA4008; 2Gérard. et al., J ClinOncol 2010;28:1638-44

  16. 1Aschele et al., J ClinOncol 2009;27:170s abstr CRA4008; 2Gérard. et al., J ClinOncol 2010;28:1638-44

  17. Conclusions: CAO/ARO/AIO-04 • 5-FU/OX-CRT with one week chemo gap • - well tolerated, high compliance • - increased pCR-rates • Quality assurance program: • - Good TME quality 74% • - Lymph nodes examined per specimen: 15 (median) • Oxaliplatinincludedbothpre- andpostop • - 73% started, 60% completed adjuvCTx in both arms • Longer follow-up needed for primary endpoint • - Disease-free survival

  18. Acknowledgement: • Supportedbythe • German CancerAid • Thanksto all thepatients, • investigatorsat 88 centers, and • data-managementstaff

More Related