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Illuminating the treatment landscape for metastatic colorectal cancer (MCRC)

Illuminating the treatment landscape for metastatic colorectal cancer (MCRC). Jean-Yves Douillard Centre René Gauducheau / CHU Laennec Nantes, France. The search for efficacy-based benefits with 5-FU/LV. 1 Advanced Colorectal Cancer Meta-Analysis Project. J Clin Oncol 1992;10:896–903

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Illuminating the treatment landscape for metastatic colorectal cancer (MCRC)

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  1. Illuminating the treatment landscape for metastatic colorectal cancer (MCRC) Jean-Yves Douillard Centre René Gauducheau/CHU LaennecNantes, France

  2. The search for efficacy-based benefits with 5-FU/LV 1Advanced Colorectal Cancer Meta-Analysis Project. J Clin Oncol 1992;10:896–903 2Poon MA et al. J Clin Oncol 1989;7:1407–18; 3de Gramont A et al. J Clin Oncol 1997;15:808–15 4Köhne CH et al. J Clin Oncol 2003;21:3721–28; 5Lokich J et al. J Clin Oncol 1989;7:425–32 6Buroker T et al. J Clin Oncol 1994;12:14–20

  3. TP-activated oral Xeloda generates 5-FU preferentially in tumor Intestine Liver Xeloda Xeloda Tumor >> healthy tissue CE 5'-DFCR 5'-DFCR CyD CyD 5'-DFUR 5'-DFUR Thymidine phosphorylase (TP) 5-FU 5'-DFCR = 5'-deoxy-5-fluorocytidine; 5'-DFUR = 5'-deoxy-5-fluorouridine; CE = carboxylesterase; CyD = cytidine deaminase

  4. First-line Xeloda in MCRC: significantly superior response rate vs bolus 5-FU/LV • The efficacy of Xeloda versus bolus 5-FU/LV was similar to infusional 5-FU/LV versus bolus 5-FU/LV TTP = time to progression Van Cutsem E et al. Br J Cancer 2004;90:1190–7

  5. Favorable safety profile of first-line Xeloda versus 5-FU/LV in MCRC Patients (%) Treatment related AEs (all grades) 100 80 60 40 20 0 Xeloda (n=596) 5-FU/LV (n=593) * * * * * Hand-foot Diarrhea Stomatitis Nausea Vomiting Alopecia Fatigue syndrome *p<0.001AE = adverse event Cassidy J et al. Ann Oncol 2002;13:566–75

  6. Synergistic or additive activity with Xeloda in preclinical models 1Sawada N et al. Clin Cancer Res 1999;5:2948–53; 2Cassidy J et al. J Clin Oncol 2004;22:2084–91 3Raymond E et al. Anticancer Drugs 1997;8:876–854Tewes M et al. Ann Oncol 2003;14:1442-8; 5Azrak RG et al. Clin Cancer Res 2004;10:1121–36Shen B-Q et al. Proc Am Assoc Cancer Res 2004;45 (Abst 2203) 7Hurwitz H et al. N Engl J Med 2004;350:2335–42; 8Tanaka Y et al. Proc Am Assoc Cancer Res 2003;44 (Abst 4678) 9Budman DR et al. Breast Cancer Res Treat 2002;76(Suppl. 1):S131 (Abst 521)

  7. Response rates with Xeloda backbonecompare favorably with 5-FU combinations Response (%) 60 50 40 30 20 10 0 XELIRI (n=52)1 FOLFIRI (n=109)2 Irinotecan/LV5FU2 (n=145)3 IFL (n=264)4 XELOX (n=96)5 FOLFOX (n=267)4 XELOX (n=50)6 FOLFOX (n=50)6 Data from phase II and III trials 1Patt YZ et al. Proc Am Soc Clin Oncol 2004;23:271 (Abst 3602)2Tournigand C et al. J Clin Oncol 2004;22:229–373Douillard JY et al. Lancet 2000;355:1041–7; 4Goldberg R et al. J Clin Oncol 2004;22:23–30 5Cassidy J et al. J Clin Oncol 2004;22:2084–91; 6Welles L et al. Proc Am Soc Clin Oncol 2004;23 (Abst 3537)

  8. Illuminating the treatment landscape for MCRC • 13.40 Lighting the way with XELOXJosep Tabernero • 14.00 X-panding patients’ options with XELIRIYehuda Patt • 14.20 A new beginning: combinations with novel biologicalsMichel Ducreux • 14.45 For a brighter future: new Xeloda combinationsHans-Joachim Schmoll • 15.10 Time for a new option: XELOX plus AvastinAxel Grothey • 15.30 CloseDavid Kerr

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