2014520 1st-lineEGFR EGFR Web2014520 URL http://www.erbitux-crc-seminar.jp/
Overview 4 VEGFEGFR FIRE-3 201414 EGFR2009 2nd-line5-FU CPT-11 CPT-11 2010 1st-line2nd-lineKRAS 1st-lineEGFR 2014 1st-lineKRAS EGFR 1 1 1. FOLFOX CapeOX Bmab FOLFIRIBmab FOLFOX Cmab Pmab FOLFIRI Cmab Pmab FOLFOXIRI FL CapeBmab or UFTLV FL CapeBmab or UFTLV FOLFIRIBmab or IRISIRI FOLFIRICmabPmab or IRICmab Pmab FOLFOX CapeOX Bmab FOLFIRIBmab or IRISIRI FOLFOX CapeOX Bmab IRICmab Pmab or CmabPmab 1st-line BSC IRICmab Pmab or CmabPmab Regorafenib or BSC IRICmab Pmab or CmabPmab Regorafenib or BSC Regorafenib or BSC Regorafenib or BSC 2nd-line BSC 1st-lineVEGF EGFR 2 2, 3, 4 2013 FIRE-3 FOLFIRIFOLFIRI 3ITT PFSp=0.18, 0.55 OSFOLFIRI 28.7FOLFIRI25.0 HR0.77p=0.0174 2 1st-lineEGFR 3rd-line Regorafenib or BSC. 2014.,, 2014; 31. KRASall RAS EGFR KRAS exon 2codon12, 13 KRAS KRAS Regorafenib or BSC 60EGFR KRAS Regorafenib or BSC KRAS exon 2 codon12, 13KRAS NRAS EGFR KRAS NRAS 10 5 5 all RAS FIRE-3RAS 2 2
RASFOLFIRI OS33.16KRAS 28.74.4 20104KRAS 2010KRAS web20145 all RAS all RAS 2. EGFRVEGF FIRE-3 KRAS 592 CALGB 80405 KRAS 1,200 PEAK KRAS 285 R Heinemann V, et al. Lancet Oncol 2014; 15: 1065-75. Venook A, et al. ASCO 2014 (Abstract LBA3) Schwartzberg LS, et al. J Clin Oncol 2014; 32: 2240-7. 3. FIRE-3 R R FOLFIRI FOLFIRI FOLFOXFOLFIRI FOLFOXFOLFIRI FOLFOXFOLFIRI 2009910 mfolfox6 mfolfox6 EGFR EGFR 69 6 7 1 1. 2014., 2014,, 31. 2Heinemann V, et al. Lancet Oncol 2014; 15: 1065-75. 3Venook A, et al. ASCO 2014; Abstract LBA3 4Schwartzberg LS, et al. J Clin Oncol 2014; 32: 2240-7. 5Douillard JY, et al. N Engl J Med 2013; 369: 1023-34. 6Van Cutsem E: Oncologist 2006; 11: 1010-7. 7Jonker D, et al. N Engl J Med 2007; 357: 2040-8. 5. all RAS KRAS 592 11 FOLFIRI 400mg/m 2 120 250mg/m 2 60 1 FOLFIRI 5mg/kg30-902 mrecist 1.0 PFS OS DpR Heinemann V, et al. Lancet Oncol 2014; 15: 1065-75. KRAS [exon 3codon 61 exon 4codon 146] NRAS KRAS 40 New RAS 10 RAS 50 Douillard JY, et al. N Engl J Med 2013; 369: 1023-34. 4. FIRE-3ITTKRAS 6. FIRE-3RAS OS FOLFIRI FOLFIRI p 62% 10.0 58% 10.3 0.18Fishers exact test 0.55Log-rank 1.0 0.75 0.50 28.7 25.0 FOLFIRIn=297 FOLFIRIn=295 =3.7 1.0 0.75 0.50 0.25 nn FOLFIRI 91171 FOLFIRI 110171 33.1 25.6 95% CI 24.5-39.4 22.7-28.6 =7.5 0.25 HR=0.77 p=0.017 Log-rank 0.0 12 24 36 48 60 72 Heinemann V, et al. Lancet Oncol 2014; 15: 1065-75. HR=0.7095% CI: 0.53-0.92 p=0.011log-rank 0.0 12 24 36 48 60 72 No. at risk 171 128 71 39 20 6 171 127 68 26 9 1 KRASNRASexon 2, 3, 4 Heinemann V, et al. Lancet Oncol 2014; 15: 1065-75. 3
EGFR8 EGFR 1 EGFR1st-line 86 71 1 12 12 1. 2nd-line 3rd-line PFS2nd-line47 78.1% 59.4% 56.3% 68.8% 40.6% 9.4% 6.25% 6.25% 3rd-line24 2-21 6-3 7-6 14-6 14-7 2-5 5 21-9 2-11 FIRE-3PFS 10.32 21.18 37.88 61.75 63.09 10.0 12 1st-line 8 0 1 2 3 4 5 6 7 8 9 10 1. Van Cutsem E. Oncologist 2006; 11: 1010-7. 1 4
strongvery strongmedium very strong21 21 1FTUfinger tip unit 1FTU0.5g 2 3FTU Grade 3 4 5 2. 4. strong very strong VG 5-7 medium very strong 3. 5. 5-FU 5
2 6. 1st-line OK 3 7 Grade 3 8 1Van Cutsem E. Oncologist 2006; 11: 1010-7. 2Maughan TS, et al. Lancet 2011; 377: 2103-14. 3Saltz LB, et al. J Clin Oncol 2008; 26: 2013-9. 4Bokemeyer C, et al. Ann Oncol 2011; 22: 1535-46. 5Hurwitz H, et al. N Engl J Med 2004; 350: 2335-42. 6Sobrero AF, et al. J Clin Oncol 2008; 26: 2311-9. 7Peeters M, et al. J Clin OncoI 2010; 28: 4706-13. 8Giantonio BJ, et al. J Clin Oncol 2007; 25: 1539-44. 9Grothey A, et al. Lancet 2013; 381: 303-12. 10Karapetis CS, et al. N Engl J Med 2008; 359: 1757-65. 11Amado RG, et al. J Clin Oncol 2008; 26: 1626-34. 12Heinemann V, et al. Lancet Oncol 2014; 15: 1065-75. 7. + Grade 3 6. 8. 6
7 1. 2. + QOL 1. UVSPF25PA QOL 1 1st-line 1st-line QOL 2 1
8 3. : 5. 4. Grade3 Grade1 Grade2 50 4C 50 2C 6. Day15 Day29 Day36 UV 3 1 1 4 1 13medium
Grade 2 Grade 3 5 6 29Grade 2 36 Grade 2 very strong Grade 3 7 7. Grade1 VG Grade2 2. Grade3 50 2C 50 4C UV 2 3 1... UV 2 3 9
MINI LECTURE 1 QOL 1QOL QOL QOL QOL 1 1 QOL QOL 2 QOL 3 QOL EGFR 1QOL CRYSTAL QOLFOLFIRIFOLFIRI Global Health StatusGHSQOL 2 4 QOL QOL QOL QOL5-FULVFOLFOX PFSFOLFOX p=0.0003 5 FOLFOXGHSQOL GHS405-FULV p=0.0004 QOL QOL Skindex-16 6 QOL1 1Fernández-Ortega P, et al. Support Care Cancer 2012; 20: 3141 8. 2Wasada I, et al. Tokai J Exp Clin Med 2013; 38: 7-11. 3Sabbatini P. Oncologist 2000; 5: 19-23. 4Láng I, et al. Eur J Cancer 2013; 49: 439-48. 5de Gramont A, et al. J Clin Oncol 2000; 18: 2938-47. 6Haley AC, et al. Support Care Cancer 2011; 19: 545-54. 1. QOL Q O L 100 80 60 40 20 0 39.3 60.7 n=539 QOLFLIE54 QOLFLIE54 44.5 55.5 n=541 Fernández-Ortega P, et al. Support Care Cancer 2012; 20: 3141-8. 2. CRYSTALQOL Global Health Status 100 FOLFIRI 90 FOLFIRI 80 70 60 50 40 30 20 95CI 10 0 10 20 8 16 24 32 40 FOLFIRI 242 226 185 146 95 61 FOLFIRI 214 227 168 149 96 82 Láng I, et al. Eur J Cancer 2013; 49: 439-48. GHSQOL 10
MINI LECTURE 2 RMT RMT Rash Management TeamRMT QOL 201011 CRCRMT RMT 1 1. RMT3 RMT RMT 1st step 2nd step 3rd step 2 RMT 2012.06.14,,,,,,,, TS-1,, GVHD 2 3 DE 4 5 Rash Management Support D E TS-1 2 2. RMT 1st Step 2nd Step 3rd Step 11