92 91 95 2016 5-FU 1 1) 2) 3) 2) 2016 1 5 2016 3 4 FOLFIRI Bevacizumab Bev 5-FU NH3 1 NH 3 5-FU NH 3 Key words: 5-FU : NH 3 orotate phosphorylase OPRT thymidylate synthase TS dihydropyrimidine dehydrogenase DPD 5-fluoro-dihydrouracil DHFU 2-F-3-ureidopropionate FUPA 5-fluoro- -alanine FBAL Ⅰ 5-FU oxaliplatin CPT-11 Bevacizumab EGFR regorafenib 2 1 5-FU FOLFOX FOLFIRI 2 5-FU 1 Ⅱ 56 16 43 CMF 5-FU 1,000 / 12 5 20XX 7 D3 moderately differentiated 1) 2) 3) Mimi Okano 1), Go Nakajima 2), Hidekazu Kuramochi 3) and Kazuhiko Hayashi 2) : A case of hyperammonemia associated with 5-FU administration for recurrent colon cancer. 1) Department of Surgery, Institute of Gastroenterology, Tokyo Women s Medical University, Tokyo 162-8666. 2) Department of Chemotherapy and Palliative Care, Tokyo Women s Medical University, Tokyo 162-8666. 3) Department of Chemotherapy, Tokyo Women s Medical University Yachiyo Medical Center, Yachiyo 276-8524. Phone: 03-3353-8111. Fax: 03-3353-8111. E-mail: puru.mimi@gmail.com Received January 5, 2016, Accepted March 4, 2016.
92 adenocarcinoma SE ly2 v2 n0 pstage KRAS 2 1 20XX 1 11 20XX 2 1 mfolfox6 l-lv 300 / L-OHP 130 / 5-FU 600 / 5-FU 3,600 / 46 2 11 7 5-FU/LV de Gramont l-lv 300 / 5-FU 600 / 5-FU 3,600 / 2 CEA 4 10 FOLFIRI l-lv / Irinotecan CPT-11 220 / 5-FU 600 / 5-FU 3,600 / 46 2 2 12 CEA 210ng/ CA19-9 1 ng/ HBs HBs HBc HBVDNA HBV HBVDNA CT 60 24 FOLFIRI Bev l-lv 200 / CPT- 11 150 / 5-FU 400 / 5-FU 2,400 / 46 Bev 5 / 2 3 grade 3 grade 2 13 2 4 2 Glasgow Coma Scale E4V3M4 NH 3 212µg/dl CT NH 3 600 / NH 3 46µg/ dl 17 FOLFIRI Bev 5 GCS E4V4M6 NH 3 305µg/dl NH 3 30µg/dl NH 3 NH 3 5-FU CT 38 19 PR 16 6 5-FU 1,000 GCSE4V4M6 NH 3 757µg/dl 5-FU CPT-11 Bev CPT-11 150 / Bev 5 / grade 2 NH 3 38µg/dl Ⅲ 5-FU orotate phosphorylase OPRT thymidylate synthase TS DNA RNA 5-FU 80 90 dihydropyrimidine dehydrogenase DPD 5-fluoro-dihydrouracil DHFU 2-F-3- ureidopropionate FUPA 5-fluoro- -alanine FBAL NH 3 FBAL fluoroacetate TCA 1
5-FU 1 93 aconitase 5-FU NH 3 FBAL Aconitase TCA 3,4 1 5 5-FU TCA 15 5-FU fluoroacetate TCA aconitase 5-FU NH 3 TCA mfolfox6 FOLFIRI 4 NH 3 NH 3 GC/MS 5-FU NH 3 5-7 3 1 5-FU NH 3 5-FU 5-FU 8 9 DPD S-1 IRIS 10 NH 3 5-FU 5-FU 5-FU NH 3 5.7 9 8 1983 2015 5-FU 24 1 68 17 : 7 mfolfox6 14 FOLFIRI 9 1 1 Day 2 3 12 3 2 NH 3 393µg/dl 9 3 2 NH 3 NH 3 5-FU NH 3 NH 3 FOLFIRI Bev 5-FU NH 3 1
94 1 NH 3 5-FU NH 3 1 2009 11 80 FOLFIRI BV 400 / bolus, 2,400 / 46 h-infusion 1 Day 3 1099 2 2009 11 56 FOLFIRI BV 400 / bolus, 2,400 / 46 h-infusion 1 Day 2 143 3 2009 6 79 FOLFOX6 200 / bolus, 2,000 / 46 h-infusion 1 Day 2 121 4 2009 7 50 ROLFIRI 400 / bolus, 2,400 / 46 h-infusion 5 Day 2 400 5 2009 12 74 FOLFOX6 400 / bolus, 2,400 / 46 h-infusion 1 Day 3 367 6 2010 4 50 FOLFOX6 400 / bolus, 2,400 / 46 h-infusion 1 Day 3 320 7 2011 13 52 FOLFOX6 400 / bolus, 2,400 / 46 h-infusion 5 Day 3 403 8 2011 13 75 FOLFOX6 BV 400 / bolus, 2,400 / 46 h-infusion 1 Day 3 352 9 2011 14 30 FOLFOX6 BV 600 / bolus, 4,000 / 46 h-infusion 5 Day 3 503 10 2012 15 69 SOX S-1 200 /body day 1-14 3 63 11 2012 15 60 FOLFOX6 400 / bolus, 2,400 / 46 h-infusion 2 Day 3 284 12 2013 16 60 FOLFOX6 400 / bolus, 2,400 / 46 h-infusion 1 Day 3 387 13 2013 10 79 FOLFIRI cetu 400 / bolus, 2,400 / 46 h-infusion 1 Day 2 1055 14 2013 8 72 FOLFOX6 400 / bolus, 2,400 / 46 h-infusion 1 Day 3 399 15 2013 17 80 FOLFIRI 320 / bolus, 1,920 / 46 h-infusion 5 Day 2 268 16 2014 18 64 FOLFOX6 400 / bolus, 3,500 / 46 h-infusion 4 Day 3 382 17 2014 19 71 FOLFOX6 BV 400 / bolus, 2,400 / 46 h-infusion 2 Day 3 381 18 2015 20 73 FOLFOX6 400 / bolus, 2,400 / 46 h-infusion 3 Day 3 387 19 2015 20 81 FOLFOX6 BV 22 Day 3 226 20 2015 20 71 FOLFIRI BV 400 / bolus, 2,400 / 46 h-infusion 5 Day 3 403 21 2015 20 60 FOLFIRI 400 / bolus, 2,400 / 46 h-infusion 1 Day 3 500 22 2015 21 50 FOLFIRI BV 400 / bolus, 2,400 / 46 h-infusion 1 Day 3 518 23 2015 22 73 FOLFOX6 400 / bolus, 2,400 / 46 h-infusion 1 Day 3 24 2016 56 FOLFIRI BV 400 / bolus, 2,400 / 46 h-infusion 4 Day 2 212 2 NH 3 SUMMARY We report a case of hyperammonemia associated with 5-FU administration during FOLFIRI bevacizumab treatment for recurrent colon cancer. Exacerbating factors and the mechanism of hyperammonemia associated with 5-FU administration have been described, but prediction remains difficult. 5-FU must be administered carefully for constipation and dehydration, and the possibility of hyperammonemia should be considered if impairment of consciousness is suspected. 1 CALGB/SWOG C80405: A phase III trial of FOLFIRI or FOLFOX with bevacizumab or cetuximab or both for untreated metastatic adenocarcinoma of the colon or rectum. Clin Adv Hematol Oncol 2006; 4: 452-3. 2 Tournigand C1, André T, Achille E, Lledo G, Flesh M, Mery-Mignard D, Quinaux E, Couteau C, Buyse M, Ganem G, Landi B, Colin P, Louvet C, de Gramont A. FOLFIRI followed by FOLFOX6 or the reverse sequence in advanced colorectal cancer: a randomized GERCOR study. J Clin Oncol 2004; 22: 229-37. 3 mfolfox6 2013; 40: 483-7. 4 5-FU FOLFOX 1 2010; 37: 1583-6. 5 Koenig H and Patel A. Biochemocal basis for fluorouracil neurotoxicity. The role of Krebs cycle inhibitor by fluoroacetate. Arch Neurol
5-FU 1 95 1970: 23; 155-60. 6 mfolfox6 1 2009; 106: 1744-50. 7 FOLFIRI 5-FU 1 2009; 36: 1167-9. 8 mfolfox6 5FU 1 2013; 74: 1162-7. 9 5-FU 2011; 104: 223-7. 10 FOLFIRI cetuximab 1 2013; 74: 1432-5. 11 FOLFIRI/ Bevacizumab 2. 2009; 69: 37-42. 12 mfolfox6 1 2009; 36: 867-9. 13 mfolfox6 2. 2011; 72: 2793-6. 14 FOLFOX 1. 2011; 64: 467-70. 15 2 2012; 39: 839-42. 16 5-FU XELOX 1 2013; 40: 2581-4. 17 FOLFIRI 5-FU 1 2013; 40: 671-3. 18 mfolfox6 1 2014; 67: 529-35. 19 mfolfox6 1 2014; 67: 285-90. 20 1 5-FU 4 2015; 112: 287-96 21 FOLFIRI IRIS 1 2015; 68: 534-7 22 5-FU 1 2015; 40: 933-7