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Xeloda Combination Therapy For MCRC

Xeloda Combination Therapy For MCRC. Xeloda plus oxaliplatin (XELOX): a solid construction. XELOX international phase II trial: first-line in MCRC (n=96). 1. 8. 15. 21. Day. Oxaliplatin 130mg/m 2 (2-hour infusion).

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Xeloda Combination Therapy For MCRC

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  1. Xeloda Combination Therapy For MCRC

  2. Xeloda plus oxaliplatin (XELOX): a solid construction

  3. XELOX international phase II trial:first-line in MCRC (n=96) 1 8 15 21 Day Oxaliplatin130mg/m2 (2-hour infusion) Xeloda1,000mg/m2 twice daily Day 1 (pm)–15 (am) Rest Repeat cycle at day 22 • Regimen recommended from phase I trial1 • Male/female (%) = 64/36; median age = 64 years2 • 28% prior (neo)adjuvant therapy 1Díaz-Rubio E et al. Ann Oncol 2002;13:558–65 2Sawada N et al. Eur J Cancer 2003;1(Suppl. 5):S93 (Abst 303)

  4. XELOX produces consistently high response rates across subgroups Patients (%) 80 60 40 20 0 61 60 60 56 55 55 55 54 53 50 Overall Liver Lung Yes No £80 >80 <60 ³60 Metastases (Neo)adjuvant KPS Age chemotherapy Sawada N et al. Eur J Cancer 2003;1(Suppl. 5):S93 (Abst 303)

  5. XELOX: median progression-freesurvival of 7.7 months (n=96) 1.0 0.8 0.6 0.4 0.2 0.0 7.7 months(95% CI: 6.4–8.6) Estimated probability 0 2 4 6 8 10 12 14 16 18 20 22 Months Sawada N et al. Eur J Cancer 2003;1(Suppl. 5):S93 (Abst 303)

  6. XELOX: median overall survival of 19.5 months (n=96) 1.0 0.8 0.6 0.4 0.2 0.0 19.5 months (95% CI: 15.3–21.6) Estimated probability 0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 Months Sawada N et al. Eur J Cancer 2003;1(Suppl. 5):S93 (Abst 303)

  7. XELOX efficacy comparesfavourably with FOLFOX4 1Sawada N et al. Eur J Cancer 2003;1(Suppl. 5):S93 (Abst 303) 2Goldberg R et al. Proc Am Soc Clin Oncol 2003;22:252 (Abst 1009)3de Gramont A et al. J Clin Oncol 2000;18:2938–47

  8. Low incidence of grade 3/4 treatment-related adverse events with XELOX Patients (%) 50 40 30 20 10 0 Grade 3 Grade 4 Laryngo-spasm* Nausea/ vomiting Fatigue/ asthenia Thrombo-cytopenia Hand-foot syndrome Sensory neuropathy Diarrhoea Neutropenia *Includes laryngopharyngeal dysesthesia Sawada N et al. Eur J Cancer 2003;1(Suppl. 5):S93 (Abst 303)

  9. XELOX: favourable safetyprofile compared with FOLFOX4 1Sawada N et al. Eur J Cancer 2003;1(Suppl. 5):S93 (Abst 303) 2Goldberg R et al. Proc Am Soc Clin Oncol 2003;22:252 (Abst 1009)3de Gramont A et al. J Clin Oncol 2000;18:2938–47

  10. Improved patient benefit of XELOX Days/patient 70 60 50 40 30 20 10 0 TTP gain with FOLFOX Days in hospital/clinic Days in hospital/clinic versus 5-FU/LV1 with FOLFOX1 with XELOX2 1de Gramont A et al. J Clin Oncol 2000;18:2938–47 2Sawada N et al. Eur J Cancer 2003;1(Suppl. 5):S93 (Abst 303)

  11. XELOX: highly effective first-line treatment for MCRC • High efficacy • overall response rate: 55% • median PFS: 7.7 months • median OS: 19.5 months • compares favourably with FOLFOX4 • Favourable safety compared with FOLFOX4 • reduced incidence of neutropenia (7% vs 42–47%) • Simplified regimen with improved convenienceover FOLFOX4

  12. Xeloda plus irinotecan (XELIRI): another solid construction

  13. XELIRI in first-line MCRC:US phase II study (n=52) • Male/female (%) = 56/44; median age = 58 years • Primary tumour = 84% colon, 12% rectum, 4% both • 14 patients 65treated at 200/750 1 8 15 21 Day Irinotecan250mg/m2i.v. Xeloda1000mg/m2 twice daily Day 1 (pm)–15 (am) Rest Repeat cycle at day 22 Patt YZ et al. Eur J Cancer 2003;1(Suppl. 5):S93 (Abst 304)

  14. Consistently high response rates with XELIRI (n=52) Patients (%) 60 50 40 30 20 10 0 52 51 50 45 42 32 30 Overall Yes No £80 >80 <60 ³60 (Neo)adjuvant KPS Age chemotherapy Patt YZ et al. Eur J Cancer 2003;1(Suppl. 5):S93 (Abst 304)

  15. Time to disease progression 7.1 months 1.0 0.8 0.6 0.4 0.2 0.0 7.1 months(95% CI: 5.0–11.1) Estimated probability 0 2 4 6 8 10 12 14 16 18 20 Months Patt YZ et al. Eur J Cancer 2003;1(Suppl. 5):S93 (Abst 304)

  16. XELIRI and FOLFIRI or IFL regimens appear to have similar efficacy 1Patt YZ et al. Eur J Cancer 2003;1(Suppl. 5):S93 (Abst 304)2Goldberg R et al. Proc Am Soc Clin Oncol 2003;22:252 (Abst 1009)3Douillard JY et al. Lancet 2000;355:1041–7

  17. XELIRI: low incidence ofgrade 3/4 adverse events Patients (%) 100 80 60 40 20 0 • No treatment-related deaths Nausea/ Diarrhoea* Hand-foot Abdominal Neutropenia vomiting syndrome* pain* *No grade 4 events Patt YZ et al. Eur J Cancer 2003;1(Suppl. 5):S93 (Abst 304)

  18. Similar safety profile in older and younger patients Patients (%) 100 80 60 40 20 0 <65 years (n=37) 65 years (n=14) Neutropenia Diarrhoea Nausea/ Abdominal Hand-foot vomiting pain syndrome Patt YZ et al. Eur J Cancer 2003;1(Suppl. 5):S93 (Abst 304)

  19. XELIRI: favourable safety profile compared with FOLFIRI or IFL regimens 1Patt YZ et al. Eur J Cancer 2003;1(Suppl. 5):S93 (Abst 304) 2Goldberg R et al. Proc Am Soc Clin Oncol 2003;22:252 (Abst 1009);3Douillard JY et al. Lancet 2000;355:1041–7

  20. XELIRI: highly active first-line treatment for MCRC • Xeloda plus 3-weekly irinotecan is highly active in first-line MCRC • response rate: 46% • median TTP: 7.1 months • median OS: 16 months • Efficacy and safety compare favourably with IFL and FOLFIRI • XELIRI is more convenient than either IFL or FOLFIRI

  21. Randomised trial evaluating two Xeloda combinations in first-line MCRC • Xeloda days 1–14 every 3 weeks plus • irinotecan days 1, 8 (CAPIRI) • oxaliplatin days 1, 8 (CAPOX) • Similar antitumour activity (144 evaluable patients) • 41% overall response rate with CAPIRI • 51% with CAPOX • Similar median progression-free (7.1 and 7.2 months) and overall survival (>17 months) • Favourable safety profiles with typical toxicity of oxaliplatin and irinotecan Grothey A et al. Eur J Cancer 2003;1(Suppl. 5):S90 (Abst 295)

  22. Oral Xeloda: the keystone of CRC therapy • Xeloda is a highly effective, tolerable and more convenient combination partner than 5-FU/LV • Xeloda is replacing 5-FU/LV as the backbone of CRC therapy

  23. Xeloda1 5-FU/LV (Saltz) 5-FU/LV (Douillard) 5-FU/LV (de Gramont) XELIRI2 IFL (Goldberg) IFL (Saltz) FOLFIRI (Douillard) XELOX3 FOLFOX (de Gramont) FOLFOX (Goldberg) IFL+ Avastin 1Twelves C. Eur J Cancer 2002;38(Suppl. 2):S15–S20 2Patt YZ et al. Eur J Cancer 2003;1(Suppl. 5):S93 (Abst 304) 3Sawada N et al. Eur J Cancer 2003;1(Suppl. 5):S93 (Abst 303) Overall survival: first-line fluoropyrimidine combination regimens ? XELOX + Avastin 0 5 10 15 20 25 Median OS (months)

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