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Xeloda versus 5-FU/LV in adjuvant colon cancer: whats your conclusion? David Kerr University of Oxford Oxford, UK.

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Presentation on theme: "Xeloda versus 5-FU/LV in adjuvant colon cancer: whats your conclusion? David Kerr University of Oxford Oxford, UK."— Presentation transcript:

1 Xeloda versus 5-FU/LV in adjuvant colon cancer: whats your conclusion? David Kerr University of Oxford Oxford, UK

2 Should Xeloda replace 5-FU/LV for the adjuvant treatment of colon cancer? Against: Axel Grothey For: Jim Cassidy

3 Against Axel Grothey Mayo Clinic Rochester, Minnesota, USA

4 Large body of evidence for 5-FU in adjuvant treatment of colon cancer 5-FU/LV (Mayo Clinic regimen) versus observation Mayo Clinic regimen versus Roswell Park regimen Bolus 5-FU/LV versus continuous infusion 5-FU/LV (LV5FU2) IFL vs Roswell Park (CALGB89803) FOLFIRI versus infused 5-FU/LV (PETACC-3, ACCORD-2) FLOX versus bolus 5-FU/LV (NSABP C-07) FOLFOX versus LV5FU2 (MOSAIC)

5 Bolus 5-FU/LV evolved as standard of care for stage III colon cancer 1 OConnell MJ et al. J Clin Oncol 1997;15:246–50 2 IMPACT investigators. Lancet 1995;345:939–44 3 Wolmark N et al. J Clin Oncol 1993;11:1879–87 MOF = lomustine (MeCCNU), vincristine, 5-FU

6 Continuous infusion versus bolus 5-FU/LV: similar efficacy, improved safety André T et al. J Clin Oncol 2003;21:2896–903 *Not significant

7 Landmark trials: recent evidence for 5-FU-based combinations 1 de Gramont A et al. Proc ASCO 2005 (Abst 3501) 2 Wolmark N et al. Proc ASCO 2005 (Abst LBA3500) 3 Saltz LB et al. J Clin Oncol 2004;22:245S (Abst 3500) 4 Van Cutsem E et al. Proc ASCO 2005 (Abst LBA8)

8 Patient management with 5-FU/LV Regular visits to hospital/clinic with i.v. regimens ensures –greater opportunity for face-to-face interaction with clinicians and nurses –reduced risk of over and under compliance

9 Critical points on Xeloda Xeloda monotherapy has always been compared with the Mayo Clinic regimen in the adjuvant and palliative settings –the most toxic way to give 5-FU/LV More appropriate comparators –in the USA: Roswell Park regimen –in Europe: LV5FU2 Question of appropriate dosing of Xeloda

10 5-FU/LV: the evidence Large body of clinical trial data for 5-FU/LV and 5-FU-based combination regimens In the 1990s, bolus 5-FU/LV became the standard of care in the adjuvant setting Infusional 5-FU/LV has similar efficacy and an improved safety profile compared with bolus 5-FU/LV Xeloda has not been tested against infusional 5-FU/LV 5-FU-based combinations with oxaliplatin have evolved as standard of care

11 For Jim Cassidy Beatson Oncology Centre Glasgow, UK

12 Evidence for Xeloda comes from two phase III trials: X-ACT and XELOXA (n=3 848) 1° endpoint: DFS Stage III, resection 8 weeks Xeloda (n=1 004) Bolus 5-FU/LV (n=983) 24 weeks Stage III colon cancer XELOX (n=937) 24 weeks Bolus 5-FU/LV (Mayo Clinic or Roswell Park) (n=924) 24 or 32 weeks 1° endpoint: DFS X-ACT XELOXA

13 Continuous infusion 5-FU/LV or Xeloda? Mayo Clinic regimen was the standard of care Superiority of infused vs bolus 5-FU/LV not shown 1 Xeloda has a significantly improved safety profile vs bolus 5-FU/LV (p<0.001) 2 In a meta-analysis in MCRC, Xeloda offers at least equivalent efficacy with superior safety vs continuous infusion 5-FU 3 1 André T et al. J Clin Oncol 2003;21:2896–903 2 Cassidy J et al. Ann Oncol 2002;13:566–75 3 Cole S et al. Proc ASCO 2005 (Abst 3591)

14 Trend to superior DFS with Xeloda (ITT) Estimated probability Absolute difference at 3 years: 3.6% Test for superiority p= year DFS Xeloda (n=1 004) 64.2% 5-FU/LV (n=983)60.6% Years HR=0.87 (95% CI: 0.75–1.00) Compared to HR upper limit 1.20, p< Cassidy J et al. J Clin Oncol 2004;22:247s (Abst 3509)

15 Grade 3 / 4 diarrhea, stomatitis, nausea, vomiting, alopecia, hand-foot syndrome, neutropenia Estimated probability of a grade 3 / 4 adverse event Months 5-FU/LV Xeloda p<0.001 Fewer and later onset of key grade 3 / 4 adverse events with Xeloda versus 5-FU/LV Cassidy J et al. J Clin Oncol 2004;22:247s (Abst 3509)

16 Oral Xeloda offers freedom without a loss of effective management Proven compliance in clinical trials Patients lead a more normal lifestyle with home-based treatment Patients prefer oral chemotherapy Patient education is a priority –time allocated before treatment begins –patients advised on side-effect management up-front –telephone follow-up Less time in hospital = more face-to-face time with family

17 Flexibility with Xeloda: 28 opportunities for modifying dose per cycle Dose modification = interrupt, delay or reduce 5-FU/LV 425 / 20mg/m 2 (i.v. bolus) Xeloda 1 250mg/m 2 twice daily (oral) Day Days 1–14 Rest Repeat cycle at day 28 am pm 28 Repeat cycle at day 21 = Administration of oral tablet at home; point at which dose modification can occur = Visit to hospital/clinic for i.v. administration

18 Xeloda has improved convenience: only nine ambulatory consultations vs 30 with 5-FU/LV Mean visits per patient Xeloda (n=995) 5-FU/LV (n=974) AE treatmentDrug administrationTotal McKendrick JJ et al. J Clin Oncol Proc ASCO 2004;23:265 (Abst 3578; poster update)

19 Replacing infused 5-FU/LV with Xeloda: less time per patient Total chair time150155–30530* *Upfront patient education

20 Net costs per patient versus 5-FU/LV (£) –2 000 –4 000 Xeloda is a uniquely dominant treatment in cancer chemotherapy: UK perspective Updated from Douillard J-Y et al. Ann Oncol 2004;15(Suppl. 3):iii73 (Abst 274PD) Total DrugsAdministrationHospitalMedications Consultations (2 721) use

21 Xeloda versus Mayo Clinic regimen in adjuvant treatment Benefits At least equivalent efficacy Trend to improved DFS + OS Improved RFS toxicity Convenience Cost savings Risks hand-foot syndrome

22 Xeloda is an ideal combination partner in the adjuvant setting 1 Schmoll H-J et al. Proc ASCO 2005 (Abst 3523) 2 André T et al. N Engl J Med 2004;350:2343–51 3 Smith R et al. Proc Am Soc Clin Oncol 2003;22 (Abst 1181; poster update)

23 Xeloda: the evidence At least as effective as 5-FU/LV for stage III colon cancer –strong trend to superior DFS, superior RFS and trend to superior OS Fewer grade 3/4 toxicities than 5-FU/LV Dosing flexibility improves side effect management Convenience of oral administration allows patients to lead a more normal lifestyle Cost effective Effective, safe and convenient combination partner, simplifying combination treatment The fluoropyrimidine of choice in the adjuvant treatment of colon cancer

24 Debate summary David Kerr University of Oxford Oxford, UK

25 The need for improved adjuvant treatment for colon cancer Adjuvant 5-FU/LV has benefits, but –considerable discrepancy between consensus recommendations and use 1 –40–50% of elderly patients (>69 years) with stage III disease do not receive adjuvant chemotherapy 2 Need for more effective and convenient regimens 1 Grothey A et al. Med Klin 2002;97:270–7 2 Hensley-Alford S et al. Proc Am Soc Clin Oncol 2003;23:748 (Abst 3008)

26 Adjuvant Xeloda: a favorable benefit/risk ratio Single-agent Xeloda is at least as effective as, and better tolerated than, 5-FU/LV –proven role in stage III –should also be considered for stage II patients –efficacy and safety benefits maintained in older patients –cost savings with improved outcomes and lifestyle Xeloda can replace 5-FU/LV as it offers the best balance of efficacy, safety and convenience for patients

27 Authorities have approved Xeloda as adjuvant treatment for colon cancer EMEA approved Xeloda (31 March 2005)... Xeloda is indicated for the adjuvant treatment of patients following surgery for stage III (Dukes stage C) colon cancer FDA approved 15 June 2005

28 Should Xeloda replace 5-FU/LV for the adjuvant treatment of colon cancer?


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