92 adenocarcinoma SE ly2 v2 n0 pstage KRAS XX XX 2 1 mfolfox6 l-lv 300 / L-OHP 130 / 5-FU 600 / 5-FU 3,600 / FU/LV de Gramont

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かずしはぎにわ
5 years ago
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1 FU 1 1) 2) 3) 2) 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 FU FOLFOX FOLFIRI 2 5-FU 1 Ⅱ CMF 5-FU 1,000 / XX 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 ) Department of Chemotherapy and Palliative Care, Tokyo Women s Medical University, Tokyo ) Department of Chemotherapy, Tokyo Women s Medical University Yachiyo Medical Center, Yachiyo Phone: Fax: puru.mimi@gmail.com Received January 5, 2016, Accepted March 4, 2016.

2 92 adenocarcinoma SE ly2 v2 n0 pstage KRAS XX XX 2 1 mfolfox6 l-lv 300 / L-OHP 130 / 5-FU 600 / 5-FU 3,600 / FU/LV de Gramont l-lv 300 / 5-FU 600 / 5-FU 3,600 / 2 CEA 4 10 FOLFIRI l-lv / Irinotecan CPT / 5-FU 600 / 5-FU 3,600 / CEA 210ng/ CA ng/ HBs HBs HBc HBVDNA HBV HBVDNA CT FOLFIRI Bev l-lv 200 / CPT / 5-FU 400 / 5-FU 2,400 / 46 Bev 5 / 2 3 grade 3 grade Glasgow Coma Scale E4V3M4 NH 3 212µg/dl CT NH / 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 PR FU 1,000 GCSE4V4M6 NH 3 757µg/dl 5-FU CPT-11 Bev CPT / Bev 5 / grade 2 NH 3 38µg/dl Ⅲ 5-FU orotate phosphorylase OPRT thymidylate synthase TS DNA RNA 5-FU dihydropyrimidine dehydrogenase DPD 5-fluoro-dihydrouracil DHFU 2-F-3- ureidopropionate FUPA 5-fluoro- -alanine FBAL NH 3 FBAL fluoroacetate TCA 1

3 5-FU 1 93 aconitase 5-FU NH 3 FBAL Aconitase TCA 3, 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 FU NH 3 5-FU 5-FU 8 9 DPD S-1 IRIS 10 NH 3 5-FU 5-FU 5-FU NH FU : 7 mfolfox6 14 FOLFIRI Day NH 3 393µg/dl NH 3 NH 3 5-FU NH 3 NH 3 FOLFIRI Bev 5-FU NH 3 1

4 94 1 NH 3 5-FU NH FOLFIRI BV 400 / bolus, 2,400 / 46 h-infusion 1 Day FOLFIRI BV 400 / bolus, 2,400 / 46 h-infusion 1 Day FOLFOX6 200 / bolus, 2,000 / 46 h-infusion 1 Day ROLFIRI 400 / bolus, 2,400 / 46 h-infusion 5 Day FOLFOX6 400 / bolus, 2,400 / 46 h-infusion 1 Day FOLFOX6 400 / bolus, 2,400 / 46 h-infusion 1 Day FOLFOX6 400 / bolus, 2,400 / 46 h-infusion 5 Day FOLFOX6 BV 400 / bolus, 2,400 / 46 h-infusion 1 Day FOLFOX6 BV 600 / bolus, 4,000 / 46 h-infusion 5 Day SOX S /body day FOLFOX6 400 / bolus, 2,400 / 46 h-infusion 2 Day FOLFOX6 400 / bolus, 2,400 / 46 h-infusion 1 Day FOLFIRI cetu 400 / bolus, 2,400 / 46 h-infusion 1 Day FOLFOX6 400 / bolus, 2,400 / 46 h-infusion 1 Day FOLFIRI 320 / bolus, 1,920 / 46 h-infusion 5 Day FOLFOX6 400 / bolus, 3,500 / 46 h-infusion 4 Day FOLFOX6 BV 400 / bolus, 2,400 / 46 h-infusion 2 Day FOLFOX6 400 / bolus, 2,400 / 46 h-infusion 3 Day FOLFOX6 BV 22 Day FOLFIRI BV 400 / bolus, 2,400 / 46 h-infusion 5 Day FOLFIRI 400 / bolus, 2,400 / 46 h-infusion 1 Day FOLFIRI BV 400 / bolus, 2,400 / 46 h-infusion 1 Day FOLFOX6 400 / bolus, 2,400 / 46 h-infusion 1 Day FOLFIRI BV 400 / bolus, 2,400 / 46 h-infusion 4 Day 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: 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: mfolfox6 2013; 40: FU FOLFOX ; 37: Koenig H and Patel A. Biochemocal basis for fluorouracil neurotoxicity. The role of Krebs cycle inhibitor by fluoroacetate. Arch Neurol

5 5-FU : 23; mfolfox ; 106: FOLFIRI 5-FU ; 36: mfolfox6 5FU ; 74: FU 2011; 104: FOLFIRI cetuximab ; 74: FOLFIRI/ Bevacizumab ; 69: mfolfox ; 36: mfolfox ; 72: FOLFOX ; 64: ; 39: FU XELOX ; 40: FOLFIRI 5-FU ; 40: mfolfox ; 67: mfolfox ; 67: FU ; 112: FOLFIRI IRIS ; 68: FU ; 40: 933-7

スライド 1

スライド 1 QOL 1 Goldberg, JCO 22:23-30, 2004 N9741: Oxaliplatin in First Line (US) IR 200 mg/m 2 OX 85 mg/m 2 every 3 weeks Efficacy IFL FOLFOX4 > IFL IROX FOLFOX4 IROX OS TTP RR 15.0 mo 6.9 mo 31 % P=0.0001 P=0.0014