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La target therapy: cosa ci aspettiamo

La target therapy: cosa ci aspettiamo. Paolo G. Casali paolo.casali@istitutotumori.mi.it. Terapia molecolare mirata. SCF. Imatinib. Imatinib chemioterapia. OS. months. 0. +2 sett. Le “differenze”. D. p <0.05. Le “differenze”. D. Le “differenze”. D. KIT. KIT (~80%) .

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La target therapy: cosa ci aspettiamo

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  1. La target therapy: cosa ci aspettiamo Paolo G. Casali paolo.casali@istitutotumori.mi.it

  2. Terapia molecolare mirata SCF Imatinib

  3. Imatinib chemioterapia OS months

  4. 0 +2 sett

  5. Le “differenze” D p <0.05

  6. Le “differenze” D

  7. Le “differenze” D

  8. KIT

  9. KIT(~80%) PDGFRA (~10%) WT (~10%) esone 9 (~10%) esone 11 (~70%) esone 13 (~5%) esone 17 (~5 %) Lasota J et al, Histopathology 2008

  10. Heinrich MC, J Clin Oncol 2003;21:4342

  11. KIT exon 9

  12. KIT esone 9 PDGFRA

  13. PDGFRA Corless CL, J Clin Oncol 2005, 23: 5357

  14. GIST in sindromi 0 – 18+ aa GIST pediatrici

  15. Neurofibromatosi, tipo 1 Mussi C, Clin Cancer Res 2008;14:4550

  16. Agaram NP et al, Clin Cancer Res 2008;14:3204

  17. Terapia molecolare mirata SCF Imatinib

  18. Negri T al, J Natl Cancer Inst 2009;101:194

  19. EORTC/ISG/AGITG #62005 Imatinib 400 mg d R Imatinib 800 mg d

  20. Casali PG et al, ECCO Ann Meet 2005

  21. “More is better”?

  22. Farmacocinetica Judson I et al, Cancer Chemother Pharmacol 2005;55:379

  23. Risposta tumorale

  24. Criteri di risposta tumorale WHO/ECOG 50% RECIST 30%

  25. Choi’s RECIST

  26. Choi’s criteria: Risposta tumorale 10% 15%

  27. -13 HU 9 HU 15 HU 36 HU 83 HU - 18 HU -34 HU -9 HU 5 HU 9 HU 52 HU 57 HU - 2 HU 61 HU 3 HU 13 HU 5 HU 20 HU 39 HU 3 HU 10 HU 57 HU

  28. Stacchiotti S et al, Radiology 2009;epub

  29. PET scan

  30. 0 +3-4 sett +12 mm +18 mm

  31. SUNITINIB 50 mg/day, 4 weeks on, 2 weeks off

  32. Van den Abbeele AD et al, ECCO Ann meet 2005

  33. Progressione intervallare

  34. t

  35. BFR14 study stop Imatinib CR PR SD R Imatinib continue Imatinib • 12 mos • surgery if feasible

  36. Resistenza secondaria

  37. CH3 O H3C CH3 N N H CH3 F N H O N H Sunitinib VEGFR-1 KIT VEGFR-2 PDGFR-a PDGFR-b VEGFR-3 FLT-3 RET

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