106 : pt1,nx,( )pt2,nx - 4 Stage II ct3,n0,m0 Stage III ct1-3,n Clinical T4b HIPEC Endorectal ultraso

Transcription

1 峯 ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) /

2 106 : pt1,nx,( )pt2,nx - 4 Stage II ct3,n0,m0 Stage III ct1-3,n Clinical T4b HIPEC Endorectal ultrasound Clinical T4b T3-4N0 pt Any,N1-2 Clinical T4b ECOG 0-1 癌症診療指引16

3 1-1 ( ) ( -7) ( -2) ( ) * ptis pt1, <0.1cm ( -7) 癌症診療指引17 * pt1 1. >0.1cm ( -2)

4 2-2 Stage I ct1-2,n0-3 CEA Colonoscopy +biopsy CXR Abdominal/pelvic CT MRI Chest CT Sigmoidoscopy + LGI series Abdominal echo PET-CT Rigid proctoscopy Endorectal ultrasound CEA Colonoscopy +biopsy ( )6 Stage II ct3,n0 or Stage III ct Any,N1-2 ct4 and/or Stage IV ct Any, N Any, M 癌症診療指引 (>11cm) (> 7cm & 11 cm) ( 7 cm ) 18 75

5 2-3 pt1, Nx Margin negative Stage I ct1-2, N0 pt1, NX pt2, Nx Stage I pt1-2, N0, M0 Stage II A pt3, N0, M0 ( ) -7 癌症診療指引19 Stage IIB~C pt4, N0, M0 Stage III pt1-4, N1-2 Risk factor(s)* SM3(Submucosa layer 3) invasion 5. StageIIA,pT3N0M0 (without risk factor) added inspection MSI or MMR (optional),if MSI low adjuvant chemotherapy

6 4-4 Stage I pt1-2,n0, M0 Stage II ct3,n0,m0 Stage III ct1-3,n1-2 T4 and/or Stage II pt3,n0, M0 or Stage III pt1-4,n1-2 Any T (*1) (*2) -7 癌症診療指引20 *1. Fluoropyrimidines ( oxaliplatin) *2. T3,N0 RT

7 5-5 or or or * Stage IV Metastases * * -7 癌症診療指引21 Stage IV RAS Mutation ( Stage Optional optional B-RAF.MSI.MMR )

8 6-6 Recurrence / Colonoscopy Chest/ abdominal+ pelvic CT Consider PET-CT Scan or * * -7 癌症診療指引22 Stage IV RAS Mutation ( Stage Optional optional :B-RAF.MSI.MMR )

9 7-7 CEA Chest /Abdomen + pelvic CT Follow up Program for Rectal Cancer Patients ( at least 5 years ) (1) High risk patients 6 eg Stage III or lymphatic or venous invasion by tumor ; poorly differentiated tumors) (2) Stage IV patients Colonoscopy or Barium enema + Sigmoidoscopy Rigid proctoscopy ( ) advanced adenoma 1 3. advance adenoma 癌症診療指引23 Abdomen sono ( ) 6 PET-CT scan ( )

10 1-1 ( ) ( -6) ( -2) ( ) * ptis pt1, <0.1cm * pt1 1. >0.1cm ( -6) ( -2) 癌症診療指引24

11 2-2 CEA Colonoscopy +Biopsy CXR Abdominal/pelvic CT MRI Chest CT Sigmoidoscopy + LGI series Abdominal echo PET-CT CEA Colonoscopy +biopsy ( )6 ptis-2, N0, M0 pt3,n0,m0 ptis-2,n0,m0 Clinical T4b pt3-4,n0 (high risk factors* pt Any, N1-2 T3-4N0 pt Any, N 癌症診療指引25 *High risk factors 1. (poorly differentiated) 2. or (lymphatic/vascular/perineural invasion) 3. <12 (<12 lymph nodes examined) 4. (localized perforation) 5. (bowel obstruction) 6. (close, indeterminate or positive margins) 7. StageIIA,pT3N0M0 (without risk factor) MSI or MMR (optional),if MSI low adjuvant chemotherapy

12 3-3 CEA Colonoscopy+ Biopsy CXR Abdominal/ pelvic CT MRI or or or * Chest CT Sigmoidoscopy + LGI series Abdominal echo PET-CT * -6 癌症診療指引26 * Stage IV RAS Mutation ( Stage Optional optional :B-RAF MSI. MMR )

13 4-4 Metastases CEA Colonoscopy +Biopsy CXR Abdominal/pelvic CT MRI KRAS gene status Chest CT Sigmoidoscopy + LGI series Abdominal echo PET-CT Needle biopsy, if clinically indicated Multidisciplinary team evaluation, including a surgeon experienced in the resection of hepatobiliary and lung metastases * * or or * -6 * Stage IV RAS Mutation ( Stage Optional optional :B-RAF MSI. MMR ) * ECOG 0-1 癌症診療指引27

14 -5 Recurrence * Chest/ abdominal/ pelvic CT Consider PET-CT Scan (2-3 ) * * -6 5 癌症診療指引28 Stage IV RAS Mutation ( Stage Optional optional :B-RAF MSI. MMR )

15 6-6 CEA Chest /Abdomen + pelvic CT Follow up Program for Rectal Cancer Patients ( at least 5 years ) (1) High risk patients 6 eg Stage III or lymphatic or venous invasion by tumor ; poorly differentiated tumors) (2) Stage IV patients Colonoscopy or Barium enema + Sigmoidoscopy Abdomen sono ( ) advanced adenoma 1 3. advance adenoma 癌症診療指引29 PET-CT scan ( )

16 1. NCCN Clinical Practice in Oncology : Rectal Cancer V NCCN Clinical Practice in Oncology : Colon Cancer V Andre T, Quinaux E, Louvet C, Colin P, Gamelin E, Bouche O, Achille E, Piedbois P, Tubiana-Mathieu N, Boutan-Laroze A, Flesch M, Lledo G, Raoul Y, Debrix I, Buyse M, de Gramont A. Phase III Study Comparing a Semimonthly With a Monthly Regimen of Fluorouracil and Leucovorin As Adjuvant Treatment for Stage II and III Colon Cancer Patients : Final Results of GERCOR C96.1. L Clin Oncol 25(24) : , André, Corrado Boni, Lamia Mounedji-Boudiaf, Matilde Navarro, Josep Tabernero, Tamas Hickish, Clare Topham, Marta Zaninelli, Philip Clingan, John Bridgewater, Isabelle Tabah-Fisch, Aimery de Gramont, for the Multicenter International Studyof Oxaliplatin / 5-Fluorouracil / Leucovorin in the Adjuvant Treatment of Colon Cancer (MOSAIC) Investigators Oxaliplatin, Fluorouracil, and Leucovorin as Adjuvant Treatment for Colon Cancer. NEJM 350 (23) : , Chris Twelves, Alfred Wong, Marek P. Nowacki, Markus Abt, Howard Burris, III, et al. Capecitabine as Adjuvant Treatment for Stage III Colon Cancer. NEJM 352(26) : , Kato T, Ohashi Y, Nakazato H, Koika A, Saji S, Suzuki H, et al. Efficacy of oral UFT as adjuvant chemotherapy to curative resection of colorectal cancer : multicenter prospective randomized trial. Langenbeck s Arch Surg 2002; 386 : Akasu T, Moriya Y, Ohashi Y, Yoshida S, Shirao K, Kodaira S. Adjuvant chemotherapy with uraciltegafur for pathological stage III rectal cancer after excision with selective lateral pelvic lymphadenectomy : a multicenter randomized controlled trial. Jpn J Clin Oncol 2006; 36 : Barry C. Lembersky, H. Samuel Wieand, Nicholas J. Petrelli, Michael J. O Connell, Linda H. Colangelo, Roy E. Smith, Thomas E. Seay, Jeffrey K. Giguere, M. Ernest Marshall, Andrew D. Jacobs, Lauren K. Colman, Atilla Soran, Greg Yothers, and Norman Wolmark. Oral Uracil and Tegafur Plus Leucovorin Compared With Intravenous Fluorouracil and Leucovorin in Stage II and III Carcinoma of the Colon : Results From National Surgical Adjuvant Breast and Bowel Project Protocol C-06. Journal of Clinical Oncology ; 24(13) : 癌症診療指引30

17 9. Daniel G. Haller, Josep Tabernero, Jean Maroun, et al. Capecitabine Plus Oxaliplatin Compared with Fluorouracil and Folinic Acid as Adjuvant Therapy for Stage III Colon Cancer. Journal of Clinical Oncology 29 : 1-9, E Bajetta,M Di Bartolomeo,R Buzzoni,et al.uracil/ftorafur/leucovorin combined with irinoteca(tegafiri) or oxaliplatin(tegafox) as 11. first-line treatment for metastatic colorectal cancer patients:results of randomised phase II study.british Journal of Cancer 96: , 2007 癌症診療指引31

18 癌症診療指引32 Adjuvant Therapy of Colon Cancer mfolfox6 mg/m 2 Oxaliplatin 85 1 Q2W Leucovorin Q2W FU Q2W FU Q2W * Continuous infusion for 24 hours FOLFOX4 mg/m 2 Oxaliplatin 85 1 Q2W 12 9 Leucovorin Q2W FU Q2W FU Q2W 12 9 * Continuous infusion for 24 hours FLOX mg/m 2 Oxaliplatin 85 1, 15, 29 Q8W 3 4 Leucovorin 500 1, 8, 15, , 36 Q8W FU 500 1, 8, 15, , 36 Q8W 3 4

19 Capecitabine 癌症診療指引33 mg/m 2 Capecitabine 1250 PO BID 1-14 Q3W 8 5 CapeOx mg/m 2 Oxaliplatin Q3W 8 6 Capecitabine 1000 PO BID 1-14 Q3W FU+LV mg/m 2 Leucovorin 500 1, 8, 15, , 36 Q8W FU 500 1, 8, 15, , 36 Q8W 4 7 slv5fu2 mg/m 2 Leucovorin Q2W FU Q2W FU Q2W 12 8 * Continuous infusion for 24 hours mg/m 2 UFUR /day PO 1-28 Q4W 6 10

20 mg/m2 癌症診療指引34 TS PO 1-28 Q42D Andre T Boni C, Mounedji-Boudiaf L, et al. Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer. N Engl J Med 2004;350: Cheeseman SL, Joel SP, Chester JD, et al. A modified de Gramont regimen of fluorouracil, alone and with oxaliplatin, for advanced colorectal cancer. Br J Cancer 2002;87: Maindrault-Goebel F, degramont A, Louvet C,et al. Evaluation of oxaliplatin dose intensity in bimonthly leucovorin and 48- hour 5-fluorouracil continuous infusion regimens (FOLFOX) in pretreated metastatic colorectal cancer. Annals of Oncology 2000;11: Kuebler JP, Wieand HS, O Connell MJ, et al. Oxaliplatin combined with weekly bolus fluorouracil and leucovorin as surgical adjuvant chemotherapy for stage II and III colon cancer: results from NSABP C-07. J Clin Oncol 2007;25: Twelves C, Wong A, Nowacki MP, et al. Capecitabine as adjuvant treatment for stage III colon cancer. N Engl J Med 2005;352: Schmoll HJ, Cartwright T, Taernero J, et al. Phase III trial of capecitabine plus oxaliplatin as adjuvant therapy for stage III colon cancer: a planned safety analysis in 1,864 patients. J Clin Oncol 2007;25: Haller DG, Catalano P, Macdonald JS Mayer RJ. Phase III study of fluorouracil, leucovorin and levamisole in high risk stage II and III colon cancer: final report of Intergroup J Clin Oncol 2005;23: Andre T, Louvet C, Maindrault-Goebel F, et al. CPT-11 (irinotecan) addition to bimonthly, high-dose leucovorin and bolus and continuous-infusion 5-fluorouracil (FOLFIRI) for pretreated metastatic colorectal cancer. Eur J Cancer 1999;35(9): degramont A, Figer A, Seymour M, et al. Leucovorin and Fluorouracil With or Without Oxaliplatin as First-Line Treatment in Advanced Colorectal Cancer. J Clon Oncol 2000;18:

21 1998;16(10): Hamaguchi, Tetsuya et al. Capecitabine versus S-1 as adjuvant chemotherapy for patients with stage III colorectal cancer (JCOG0910): an open-label, non-inferiority, randomised, phase 3, multicentre trial. The Lancet Gastroenterology & Hepatology, Volume 3, Issue 1, Sulkes A, Benner SE, Canetta RM. Uracil-ftorafur: an oral fluoropyrimidine active in colorectal cancer. J Clin Oncol. Oct 10. 癌症診療指引35

22 Therapy of Rectal Cancer Adjuvant 癌症診療指引36 Chemotherapy mfolfox6 mg/m 2 Oxaliplatin 85 1 Q2W Leucovorin Q2W 12 5-FU Q2W 12 5-FU Q2W 12 * Continuous infusion for 24 hours slv5fu2 mg/m 2 Leucovorin Q2W 12 4, 13 5-FU Q2W 12 5-FU Q2W 12 * Continuous infusion for 24 hours Capecitabine mg/m 2 Capecitabine 1250 PO BID 1-14 Q3W 8 5 CapeOx mg/m 2 Oxaliplatin Q3W 8 6, 7 Capecitabine 1000 PO BID 1-14 Q3W 8

23 5-FU+LV 癌症診療指引37 mg/m 2 Leucovorin 500 1, 8, 15, , 36 Q8W FU 500 1, 8, 15, , 36 Q8W 4 mg/m 2 UFUR /day PO 1-28 Q4W 6 14 mg/m 2 TS mg PO BID 1-28 Q42D 4 15 Chemotherapy + RT XRT + continuous infusion 5-FU mg/m 2 5-FU or 1-7 Q4W During XRT 9 XRT + 5-FU/LV mg/m 2 5-FU Q4W During week 1, 5 of XRT 10 Leucovorin Q4W

24 + Capecitabine XRT 癌症診療指引38 mg/m 2 Capecitabine 825 PO BID 1-5 QW 5 11, 12 XRT + mfolfox6 mg/m 2 Oxaliplatin 85 1 Leucovorin FU FU * Continuous infusion for 24 hours 1. Andre T Boni C, Mounedji-Boudiaf L, et al. Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer. N Engl J Med 2004;350: Cheeseman SL, Joel SP, Chester JD, et al. A modified de Gramont regimen of fluorouracil, alone and with oxaliplatin, for advanced colorectal cancer. Br J Cancer 2002;87: Maindrault-Goebel F, degramont A, Louvet C,et al. Evaluation of oxaliplatin dose intensity in bimonthly leucovorin and 48- hour 5-fluorouracil continuous infusion regimens (FOLFOX) in pretreated metastatic colorectal cancer. Annals of Oncology 2000;11: Andre T, Louvet C, Maindrault-Goebel F, et al. CPT-11 (irinotecan) addition to bimonthly, high-dose leucovorin and bolus and continuous-infusion 5-fluorouracil (FOLFIRI) for pretreated metastatic colorectal cancer. Eur J Cancer 1999;35(9):

25 Twelves C, Wong A, Nowacki MP, et al. Capecitabine as adjuvant treatment for stage III colon cancer. N Engl J Med 5. 癌症診療指引 ;352: Schmoll HJ, Cartwright T, Taernero J, et al. Phase III trial of capecitabine plus oxaliplatin as adjuvant therapy for stage III colon cancer: a planned safety analysis in 1,864 patients. J Clin Oncol 2007;25: Haller DG, Tabernero J, Maroun J, et al. Capecitabine Plus Oxaliplatin Compared With Fluorouracil and Folinic Acid As Adjuvant Therapy for Stage III Colon Cancer. J Clin Oncol 2011;29: Petrelli N, Douglass Jr HO, Herrare L, et al. The modulation of fluorouracil with leucovorin in metastatic colorectal carcinoma: 40 a prospective randomized phase III trial. J Clin Oncol 1989;7: O Connell MJ, Martenson JA, Wieand HS, et al. Improving adjuvant therapy for rectal cancer by combining protracted-infusion fluorouracil with radiation therapy after curative surgery. N Engl J Med 1994;331: Tepper JE, O Connell M, Niedzwiecki D, et al. Adjuvant therapy in rectal cancer: analysis of stage, sex, and local control final report of Intergroup J Clin Oncol 2002;20: O Connell MJ, Colangelo LH, Beart RW, et al. Capecitabine and oxaliplatin in the preoperative multimodality treatment of rectal cancer: surgical end points from National Surgical Adjuvant Breast and Bowel Project trial R-04. J Clin Oncol 2014;32: Hofheinz R, Wenz FK, Post S, et al. Chemoradiotherapy with capecitabine versus fluorouracil for locally advanced rectal cancer: A randomized, multicenter, non-inferiority, phase 3 trial. Lancet Oncol 2012;13: Shikina A, Shinto E, Hashiguchi Y, et al. Differential clinical benefits of 5-fluorouracil-based adjuvant chemotherapy for patients with stage III colorectal cancer according to CD133 expression status. Jpn J Clin Oncol. Jan 2014;44(1): Sulkes A, Benner SE, Canetta RM. Uracil-ftorafur: an oral fluoropyrimidine active in colorectal cancer. J Clin Oncol. Oct 1998;16(10): Hamaguchi, Tetsuya et al. Capecitabine versus S-1 as adjuvant chemotherapy for patients with stage III colorectal cancer (JCOG0910): an open-label, non-inferiority, randomised, phase 3, multicentre trial. The Lancet Gastroenterology & Hepatology, Volume 3, Issue 1,

26 for Advanced or Metastatic Colon and Rectal Cancer Chemotherapy 癌症診療指引40 First-line therapy mfolfox6 or mfolfox7 mg/m 2 Oxaliplatin 85 1 Q2W , 2, 3, 28 Leucovorin Q2W FU (optional) Q2W FU Q2W 8-12 * Continuous infusion for 24 hours FOLFOX + Bevacizumab mg/m 2 Bevacizumab 5 mg/kg 1 Q2W 4 Oxaliplatin 85 1 Q2W Leucovorin Q2W 5-FU (optional) Q2W 5-FU Q2W * Continuous infusion for 24 hours

27 + Panitumumab (KRAS/NRAS WT gene only) FOLFOX 癌症診療指引41 mg/m 2 Panitumumab 6 mg/kg 1 Q2W 5 Oxaliplatin 85 1 Q2W Leucovorin Q2W 5-FU (optional) Q2W 5-FU Q2W * Continuous infusion for 24 hours FOLFOX + Cetuximab (KRAS/NRAS WT gene only) mg/m 2 Cetuximab 500 ( ) 1 Q2W (QW) 6 Oxaliplatin 85 1 Q2W Leucovorin Q2W 5-FU (optional) Q2W 5-FU Q2W * Continuous infusion for 24 hours CapeOx mg/m 2 Oxaliplatin Q3W Max 16 7 Capecitabine PO BID 1-14 Q3W Max 16

28 + Bevacizumab CapeOx 癌症診療指引42 mg/m 2 Bevacizumab 7.5 mg/kg 1 Q3W Max 16 7 Oxaliplatin Q3W Max 16 Capecitabine PO BID 1-14 Q3W Max 16 FOLFIRI mg/m 2 Irinotecan Q2W 8, 9 Leucovorin Q2W 5-FU (optional) Q2W 5-FU Q2W * Continuous infusion for 24 hours FOLFIRI + Bevacizumab mg/m 2 Bevacizumab 5 mg/kg 1 Q2W 10 Irinotecan Q2W Leucovorin Q2W 5-FU (optional) Q2W 5-FU Q2W * Continuous infusion for 24 hours

29 + Cetuximab (KRAS/NRAS WT gene only) FOLFIRI 癌症診療指引43 mg/m 2 Cetuximab 500 ( ) 1 Q2W (QW) 11, 12 Irinotecan Q2W Leucovorin Q2W 5-FU (optional) Q2W 5-FU Q2W * Continuous infusion for 24 hours FOLFIRI + Panitumumab (KRAS/NRAS WT gene only) mg/m 2 Panitumumab 6 mg/kg 1 Q2W 13 Irinotecan Q2W Leucovorin Q2W 5-FU (optional) Q2W 5-FU Q2W * Continuous infusion for 24 hours Capecitabine mg/m 2 Capecitabine PO BID 1-14 Q3W 5

30 + Bevacizumab Capecitabine 癌症診療指引44 mg/m 2 Bevacizumab 7.5 mg/kg 1 Q3W 16 Capecitabine PO BID 1-14 Q3W FOLFOXIRI Bevacizumab mg/m 2 Bevacizumab 5 mg/kg 1 Q2W 21, 22 Oxaliplatin 85 1 Q2W Irinotecan Q2W Leucovorin Q2W 5-FU Q2W * Continuous infusion for 24 hours Cetuximab (KRAS/NRAS WT gene only) mg/m 2 Cetuximab 500 ( ) 1 Q2W (QW) 12, 25 Panitumumab (KRAS/NRAS WT gene only) mg/m 2 Panitumumab 6 mg/kg 1 Q2W 26 Pembrolizumab (MSI-H)

31 mg/m2 癌症診療指引45 Pembrolizumab 2 mg/kg 1 Q3W 30 Nivolumab (MSI-H) mg/m 2 Nivolumab 3 mg/kg 1 Q2W 31 Nivolumab (MSI-H) mg/m 2 Nivolumab 240 mg 1 Q2W 31 Bolus or Infusional 5FU/Leucovorin Roswell Park mg/m 2 Leucovorin 500 1, 8, 15, 22, 29, 36 Q8W 17 5-FU 500 1, 8, 15, 22, 29, 36 Q8W Simplified biweekly infusional 5-FU/LV (slv5fu2) mg/m 2 Leucovorin Q2W 8 5-FU Q2W 5-FU Q2W

32 Weekly 癌症診療指引46 mg/m 2 Leucovorin 20 1 QW 18 5-FU QW mg/m 2 Leucovorin QW 19 5-FU QW Second-line and other therapy FOLFIRI + Ziv-aflibercept mg/m 2 Ziv-aflibercept 4 mg/kg 1 Q2W 14 Irinotecan Q2W Leucovorin Q2W 5-FU (optional) Q2W 5-FU Q2W * Continuous infusion for 24 hours

33 + Ramucirumab FOLFIRI 癌症診療指引47 mg/m 2 Ramucirumab 8 mg/kg 1 Q2W 15 Irinotecan Q2W Leucovorin Q2W 5-FU (optional) Q2W 5-FU Q2W * Continuous infusion for 24 hours IROX mg/m 2 Oxaliplatin 85 1 Q3W 20 Irinotecan Q3W Irinotecan mg/m 2 Irinotecan 125 (180) ( ) 1, 8 (1) Q3W (Q2W)(Q3W) 23, 24 Cetuximab (KRAS/NRAS WT gene only) + Irinotecan mg/m 2 Cetuximab 500 ( ) 1 Q2W (QW) 12, 25 Irinotecan 125 (180) ( ) 1, 8 (1) Q3W (Q2W)(Q3W)

34 Regorafenib 癌症診療指引48 mg/m 2 Regorafenib 160 mg PO 1-21 Q4W 27 mg/m 2 UFUR 200mg PO BID/TID 1-28 Q4W 32 mg/m 2 TS mg PO BID 1-28 Q42D degramont A, Figer A, Seymour M, et al. Leucovorin and Fluorouracil With or Without Oxaliplatin as First-Line Treatment in Advanced Colorectal Cancer. J Clon Oncol 2000;18: Cheeseman SL, Joel SP, Chester JD, et al. A 'modified de Gramont' regimen of fluorouracil, alone and with oxaliplatin, for advanced colorectal cancer. Br J Cancer 2002;87: Maindrault-Goebel F, degramont A, Louvet C, et al. Evaluation of oxaliplatin dose intensity in bimonthly leucovorin and 48-hour 5-fluorouracil continuous infusion regimens (FOLFOX) in pretreated metastatic colorectal cancer. Ann Oncol 2000;11: Emmanouiliders C, Sfakiotaki G, Androulakis N, et al. Front-line Bevacizumab in combination with Oxaliplatin, Leucovorin and 5-Fluorouracil (FOLFOX) in patients with metastatic colorectal cancer: a multicenter phase II study. BMC Cancer 2007;7: Douillard JY, Siena S, Cassidy J, et al. Randomized, Phase III Trial of Panitumumab With Infusional Fluorouracil, Leucovorin, and Oxaliplatin (FOLFOX4) Versus FOLFOX4 Alone As First-Line Treatment in Patients With Previously Untreated Metastatic Colorectal Cancer: The PRIME Study. J Clin Oncol 2010;28: Venook AP, Niedzwiecki D, Lenz H-J, et al. CALGB/SWOG 80405: Phase III trial of irinotecan/5-fu/leucovorin (FOLFIRI) or

35 (mfolfox6) with bevacizumab (BV) or cetuximab (CET) for patients (pts) with KRAS wild-type (wt) oxaliplatin/5-fu/leucovorin 癌症診療指引49 untreated metastatic adenocarcinoma of the colon or rectum [abstract]. ASCO Meeting Abstracts 2014;32:LBA3. 7. Saltz LB, Clarke S, Diaz-Rubio E, et al. Bevacizumab in Combination With Oxaliplatin-Based Chemotherapy As First-Line Therapy in Metastatic Colorectal Cancer: A Randomized Phase III Study. J Clin Oncol 2008;26: Andre T, Louvet C, Maindrault-Goebel F, et al. CPT-11 (Irinotecan) addition to bimonthly, high-dose leucovorin and bolus and continuous-infusion 5-fluorouracil (FOLFIRI) for pretreated metastatic colorectal cancer. Eur J Cancer 1999;35(9): Fuchs CS, Marshall J, Mitchell E, et al. Randomized, Controlled Trial of Irinotecan Plus Infusional, Bolus, or Oral Fluoropyrimidines in First-Line Treatment of Metastatic Colorectal Cancer: Results From the BICC-C Study. J Clin Oncol 2007;25: Heinemann V, von Weikersthal LF, Decker T, et al. FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab as first-line treatment for patients with metastatic colorectal cancer (FIRE-3): a randomised, open-label, phase 3 trial. Lancet Oncol Cunningham D, Humblet Y, Siena S, et al. Cetuximab Monotherapy and Cetuximab plus Irinotecan in Irinotecan-Refractory Metastatic Colorectal Cancer. N Engl J Med 2004;351: Martin-Martorell P, Rosello' S, Rodriguez-Braun E, et al. Biweekly cetuximab and irinotecan in advanced colorectal cancer 50 patients progressing after at least one previous line of chemotherapy: results of a phase II single institution trial. Br J Cancer 2008;99: Peeters M, Prince TJ, Cervantes A, et al. Randomized Phase III Study of Panitumumab With Fluorouracil, Leucovorin, and Irinotecan (FOLFIRI) Compared With FOLFIRI Alone As Second-Line Treatment in Patients With Metastatic Colorectal Cancer. J Clin Oncol 2010;28: Van Cutsem E, Tabemero J, Lakomy R, et al. Addition of Aflibercept to Fluorouracil, Leucovorin, and Irinotecan Improves Survival in a Phase III Randomized Trial in Patients With Metastatic Colorectal Cancer Previously Treated With an Oxaliplatin- Based Regimen. J Clin Oncol 2012;30: Tabernero J, Yoshino T, Cohn AL, et al. Ramucirumab versus placebo in combination with second-line FOLFIRI in patients with metastatic colorectal carcinoma that progressed during or after first-line therapy with bevacizumab, oxaliplatin, and a fluoropyrimidine (RAISE): a randomized, double-blind, multicentre, phase 3 study. Lancet Oncol 2015;16: Cunningham D, Lang I, Marcuello E, et al. Bevacizumab plus capecitabine versus capecitabine alone in elderly patients with

36 untreated metastatic colorectal cancer (AVEX): an open-label, randomised phase 3 trial. Lancet Oncol 2013;14:1077- previously 癌症診療指引 Wolmark N, Rockette H, Fisher B, et al. The benefit of leucovorin-modulated fluorouracil as postoperative adjuvant therapy for primary colon cancer: results from National Surgical Adjuvant Breast and Bowel Project protocol C-03. J Clin Oncol 1993;11: Jäger E, Heike M, Bemhard H, et al. Weekly high-dose leucovorin versus low-dose leucovorin combined with fluorouracil in advanced colorectal cancer: results of a randomized multicenter trial. J Clin Oncol 1996;14: Douillard JY, Cunningham D, Roth AD, et al. Irinotecan combined with fluorouracil compared with fluorouracil alone as first-line treatment for metastatic colorectal cancer: a multicentre randomised trial. The Lacncet 2000;355: Haller DG, Rothenberg ML, Wong AO, et al. Oxaliplatin Plus Irinotecan Compared With Irinotecan Alone as Second-Line Treatment After Single-Agent Fluoropyrimidine Therapy for Metastatic Colorectal Carcinoma. J Clin Oncol 2008;26: Falcone A, Ricci S, Brunetti I, et al. Phase III Trial of Infusional Fluorouracil, Leucovorin, Oxaliplatin, and Irinotecan (FOLFOXIRI) Compared With Infusional Fluorouracil, Leucovorin, and Irinotecan (FOLFIRI) As First-Line Treatment for Metastatic Colorectal Cancer: The Gruppo Oncologico Nord Ovest. J Clin Oncol 2007;25(13): Cremolini C, Loupakis F, Antoniotti C, et al. FOLFOXIRI plus bevacizumab versus FOLFIRI plus bevacizumab as first-line treatment of patients with metastatic colorectal cancer: updated overall survival and molecular subgroup analyses of the openlabel, phase 3 TRIBE study. Lancet Oncol 2015;16: Cunningham D, Pyrhonen S, James R, et al. Randomised trial of irinotecan plus supportive care versus supportive care alone after fluorouracil failure for patients with metastatic colorectal cancer. The Lancet 1998;352: Fuchs CS, Moore MR, Harker G, et al. Phase III Comparison of Two Irinotecan Dosing Regimens in Second-Line Therapy of Metastatic Colorectal Cancer. J Clin Oncol 2003;21: Van Cutsem E, Tejpar S, Vanbeckevoort D, et al. Intrapatient Cetuximab Dose Escalation in Metastatic Colorectal Cancer According to the Grade of Early Skin Reactions: The Randomized EVEREST Study. J Clin Oncol 2012;30: Van Custem E, Peeters M, Siena S, et al. Open-Label Phase III Trial of Panitumumab Plus Best Supportive Care Compared With

37 Supportive Care Alone in Patients With Chemotherapy-Refractory Metastatic Colorectal Cancer. J Clin Oncol 2007;25:1658- Best 癌症診療指引 Grothey A, Van Custem E, Sobrero A, et al. Regorafenib monotherapy for previously treated metastatic colorectal cancer (CORRECT): an international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet 2013;381: Hochster HS, Grothey A, Hart L, et al. Improved time to treatment failure with an intermittent oxaliplatin strategy: results of CONcePT. Ann Oncol 2014;25: Andre T, Louvet C, Maindrault-Goebel F, et al. CPT-11 (irinotecan) addition to bimonthly, high-dose leucovorin and bolus and continuous-infusion 5-fluorouracil (FOLFIRI) for pretreated metastatic colorectal cancer. Eur J Cancer 1999;35(9): Le DT, Uram JN, Wang H, et al. PD-1 Blockade in Tumors with Mismatch-Repair Deficiency. N Engl J Med. Jun ;372(26): Overman MJ KS, McDermott RS, et al. Nivolumab {+/-} ipilimumab in treatment of patients with metastatic colorectal cancer (mcrc) with and without high microsatellite instability (MSI-H): CheckMate-142 interim results [abstract]. ASCO Meeting Abstracts 2016;34: Product Information: UFUR Capsule. tegafur, uracil oral capsules Product Information: TS-1 capsules. Tegafur, Gimeracil, Oteracil potassium oral capsules

38 1. / / 1. 45~60 Gy ~2.0 Gy : 1. NCCN clinical practice guidelines in oncology-rectal cancer. version RTOG anorectal contouring ATLAS 3. S. Roels, et al. Definition and delineation of the clinical target volume for rectal cancer. Int J Oncol Biol Phys 2006; 65: Sauer R, Liersch T, Merkel S, et al. Preoperatorative Versus postoperative Chemoradiotherapy for Locally Advanced Rectal Cancer: Results of the German CAO/ARO/AIO-94 Randomized Phase III Trial After a Median Follow-UP of 11 Years. J Clin Oncol 2012; 30: 癌症診療指引52