レンバチニブ投与中の二峰性の疲労感に対してカルニチン補充療法が有用であった進行肝細胞癌の1例
症例は55歳女性．進行肝細胞癌に対してレンバチニブ8 mg/日の投与を開始した．投与開始時，疲労感はグレード0，血中アシルカルニチン/フリーカルニチン（AC/FC）比は0.158であった．投与8週目にグレード2の疲労感が出現し，AC/FC比は0.233に上昇した．レボカルニチン製剤1500 mg/日開始となり，4週後に疲労感はグレード0に改善した．その7カ月後バルプロ酸が開始となり，その4週後にはグレード2の疲労感の増悪あり，AC/FC比は0.432に上昇した．レボカルニチン製剤3000 mg/日に増量し，翌月には疲労感はグレード1に改善した．その後ソラフェニブに薬剤変更するまでの計約12カ月...
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| Published in | 肝臓 Vol. 61; no. 12; pp. 715 - 721 |
|---|---|
| Main Authors | , , , , , , , , , , |
| Format | Journal Article |
| Language | Japanese |
| Published |
一般社団法人 日本肝臓学会
01.12.2020
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| Subjects | |
| Online Access | Get full text |
| ISSN | 0451-4203 1881-3593 |
| DOI | 10.2957/kanzo.61.715 |
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| Abstract | 症例は55歳女性．進行肝細胞癌に対してレンバチニブ8 mg/日の投与を開始した．投与開始時，疲労感はグレード0，血中アシルカルニチン/フリーカルニチン（AC/FC）比は0.158であった．投与8週目にグレード2の疲労感が出現し，AC/FC比は0.233に上昇した．レボカルニチン製剤1500 mg/日開始となり，4週後に疲労感はグレード0に改善した．その7カ月後バルプロ酸が開始となり，その4週後にはグレード2の疲労感の増悪あり，AC/FC比は0.432に上昇した．レボカルニチン製剤3000 mg/日に増量し，翌月には疲労感はグレード1に改善した．その後ソラフェニブに薬剤変更するまでの計約12カ月間レンバチニブ初期投与量継続が可能であった．レンバチニブ起因性の疲労感はカルニチン欠乏症が関与している可能性があること，その際にはカルニチン補充療法が有用であることが示唆された． |
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| AbstractList | 症例は55歳女性．進行肝細胞癌に対してレンバチニブ8 mg/日の投与を開始した．投与開始時，疲労感はグレード0，血中アシルカルニチン/フリーカルニチン（AC/FC）比は0.158であった．投与8週目にグレード2の疲労感が出現し，AC/FC比は0.233に上昇した．レボカルニチン製剤1500 mg/日開始となり，4週後に疲労感はグレード0に改善した．その7カ月後バルプロ酸が開始となり，その4週後にはグレード2の疲労感の増悪あり，AC/FC比は0.432に上昇した．レボカルニチン製剤3000 mg/日に増量し，翌月には疲労感はグレード1に改善した．その後ソラフェニブに薬剤変更するまでの計約12カ月間レンバチニブ初期投与量継続が可能であった．レンバチニブ起因性の疲労感はカルニチン欠乏症が関与している可能性があること，その際にはカルニチン補充療法が有用であることが示唆された． |
| Author | 斉藤, 紘昭 今, 一義 椎名, 秀一朗 山形, 亘 大久保, 捷奇 山科, 俊平 石塚, 敬 池嶋, 健一 永原, 章仁 大久保, 裕直 伊藤, 顕太郎 |
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| References | 19) Lheureux PE, Penaloza A, Zahir S, et al. Science review: carnitine in the treatment of valproic acid-induced toxicity - what is the evidence? Crit Care 2005; 9: 431-440 8) Mendoza TR, Wang XS, Cleeland CS, et al. The rapid assessment of fatigue severity in cancer patients: Use of the brief fatigue inventory. Cancer 1999; 85: 1186-1196 4) Sho T, Suda G, Ogawa K, et al. Early response and safety of lenvatinib for patients with advanced hepatocellular carcinoma in a real-world setting. JGH Open 2019; 4: 54-60 15) Tamai I, Ohashi R, Nezu J, et al. Molecular and functional identification of sodium ion-dependent, high affinity human carnitine transporter OCTN2. J Biol Chem 1998; 273: 20378-20382 16) Hu C, Lancaster CS, Zuo Z, et al. Inhibition of OCTN2-mediated transport of carnitine by etoposide. Mol Cancer Therap 2012; 11: 921-929 9) Nishikawa H, Shiraki M, Hiramatsu A, et al. Japan Society of Hepatology Guidelines for Sarcopenia in Liver Disease (1st Edition): Recommendation From the Working Group for Creation of Sarcopenia Assessment Criteria. Hepatol Res 2016; 46: 951-963 2) Hiraoka A, Kumada T, Atsukawa M, et al. Prognostic factor of lenvatinib for unresectable hepatocellular carcinoma in real-world conditions-Multicenter analysis. Cancer Med 2019; 8: 3719-3728 7) Okuyama T, Wang XS, Akechi T, et al. Validation study of the Japanese version of the brief fatigue inventory. J Pain Symptom Manage 2003; 25: 106-117 12) Mohandas H, Jaganathan SK, Mani MP, et al. Cancer-related fatigue treatment: An overview. J Cancer Res Ther 2017; 13: 916-929 1) Obi S, Sato T, Sato S, et al. The efficacy and safety of lenvatinib for advanced hepatocellular carcinoma in a real-world setting. Hepatol Int 2019; 13: 199-204 14) Stanley CA. Carnitine deficiency disorders in children. Ann N Y Acad Sci 2004; 1033: 42-51 6) Sztajnkrycer MD. Valproic acid toxicity: overview and management. J Toxicol Clin Toxicol 2002; 40: 789-801 18) Kudo M, Finn RS, Qin S, et al. Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 non-inferiority trial. Lancet 2018; 391: 1163-1173 3) Hatanaka T, Kakizaki S, Nagashima T, et al. Analyses of Objective Response Rate, Progression-Free Survival, and Adverse Events in Hepatocellular Carcinoma Patients Treated With Lenvatinib: A Multicenter Retrospective Study. Hepatol Res 2020; 50: 382-395 13) 日本小児医療保健協議会栄養委員会. 「カルニチン欠乏症の診断・治療指針」2018, p4 20) Endo K, Ueno T, Ishikawa K, et al. Auris Effects of l-carnitine administration on health-related quality of life during cisplatin-based chemoradiotherapy in patients with head and neck squamous cell carcinoma. Nasus Larynx 2019; 46: 431-436 10) Takahashi A, Moriguchi M, Seko Y, et al. Impact of relative dose intensity of early-phase lenvatinib treatment on therapeutic response in hepatocellular carcinoma. Anticancer Res 2019; 39: 5149-5156 5) Khan HA, Alhomida AS. A review of the logistic role of L-carnitine in the management of radiation toxicity and radiotherapy side effects. J Appl Toxicol 2011; 31: 707-713 11) Eso Y, Nakano S, Mishima M, et al. Dose intensity/body surface area ratio is a novel marker useful for predicting response to lenvatinib against hepatocellular carcinoma. Cancers (Basel) 2019 Dec 22; 12 (1). pii: E49. doi: 10.3390/cancers12010049 21) Cruciani RA, Zhang JJ, Manola J, et al. L-carnitine supplementation for the management of fatigue in patients with cancer: an eastern cooperative oncology group phase III, randomized, double-blind, placebo-controlled trial. J Clin Oncol 2012; 30: 3864-3869 17) Okubo H, Ando H, Ishizuka K, et al. Carnitine insufficiency is associated with fatigue during lenvatinib treatment in patients with hepatocellular carcinoma. PLoS One 2020; 15: e0229772 |
| References_xml | – reference: 20) Endo K, Ueno T, Ishikawa K, et al. Auris Effects of l-carnitine administration on health-related quality of life during cisplatin-based chemoradiotherapy in patients with head and neck squamous cell carcinoma. Nasus Larynx 2019; 46: 431-436 – reference: 21) Cruciani RA, Zhang JJ, Manola J, et al. L-carnitine supplementation for the management of fatigue in patients with cancer: an eastern cooperative oncology group phase III, randomized, double-blind, placebo-controlled trial. J Clin Oncol 2012; 30: 3864-3869 – reference: 15) Tamai I, Ohashi R, Nezu J, et al. Molecular and functional identification of sodium ion-dependent, high affinity human carnitine transporter OCTN2. J Biol Chem 1998; 273: 20378-20382 – reference: 18) Kudo M, Finn RS, Qin S, et al. Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 non-inferiority trial. Lancet 2018; 391: 1163-1173 – reference: 2) Hiraoka A, Kumada T, Atsukawa M, et al. Prognostic factor of lenvatinib for unresectable hepatocellular carcinoma in real-world conditions-Multicenter analysis. Cancer Med 2019; 8: 3719-3728 – reference: 7) Okuyama T, Wang XS, Akechi T, et al. Validation study of the Japanese version of the brief fatigue inventory. J Pain Symptom Manage 2003; 25: 106-117 – reference: 16) Hu C, Lancaster CS, Zuo Z, et al. Inhibition of OCTN2-mediated transport of carnitine by etoposide. Mol Cancer Therap 2012; 11: 921-929 – reference: 8) Mendoza TR, Wang XS, Cleeland CS, et al. The rapid assessment of fatigue severity in cancer patients: Use of the brief fatigue inventory. Cancer 1999; 85: 1186-1196 – reference: 11) Eso Y, Nakano S, Mishima M, et al. Dose intensity/body surface area ratio is a novel marker useful for predicting response to lenvatinib against hepatocellular carcinoma. Cancers (Basel) 2019 Dec 22; 12 (1). pii: E49. doi: 10.3390/cancers12010049 – reference: 14) Stanley CA. Carnitine deficiency disorders in children. Ann N Y Acad Sci 2004; 1033: 42-51 – reference: 9) Nishikawa H, Shiraki M, Hiramatsu A, et al. Japan Society of Hepatology Guidelines for Sarcopenia in Liver Disease (1st Edition): Recommendation From the Working Group for Creation of Sarcopenia Assessment Criteria. Hepatol Res 2016; 46: 951-963 – reference: 1) Obi S, Sato T, Sato S, et al. The efficacy and safety of lenvatinib for advanced hepatocellular carcinoma in a real-world setting. Hepatol Int 2019; 13: 199-204 – reference: 10) Takahashi A, Moriguchi M, Seko Y, et al. Impact of relative dose intensity of early-phase lenvatinib treatment on therapeutic response in hepatocellular carcinoma. Anticancer Res 2019; 39: 5149-5156 – reference: 13) 日本小児医療保健協議会栄養委員会. 「カルニチン欠乏症の診断・治療指針」2018, p4 – reference: 19) Lheureux PE, Penaloza A, Zahir S, et al. Science review: carnitine in the treatment of valproic acid-induced toxicity - what is the evidence? Crit Care 2005; 9: 431-440 – reference: 6) Sztajnkrycer MD. Valproic acid toxicity: overview and management. J Toxicol Clin Toxicol 2002; 40: 789-801 – reference: 17) Okubo H, Ando H, Ishizuka K, et al. Carnitine insufficiency is associated with fatigue during lenvatinib treatment in patients with hepatocellular carcinoma. PLoS One 2020; 15: e0229772 – reference: 5) Khan HA, Alhomida AS. A review of the logistic role of L-carnitine in the management of radiation toxicity and radiotherapy side effects. J Appl Toxicol 2011; 31: 707-713 – reference: 12) Mohandas H, Jaganathan SK, Mani MP, et al. Cancer-related fatigue treatment: An overview. J Cancer Res Ther 2017; 13: 916-929 – reference: 3) Hatanaka T, Kakizaki S, Nagashima T, et al. Analyses of Objective Response Rate, Progression-Free Survival, and Adverse Events in Hepatocellular Carcinoma Patients Treated With Lenvatinib: A Multicenter Retrospective Study. Hepatol Res 2020; 50: 382-395 – reference: 4) Sho T, Suda G, Ogawa K, et al. Early response and safety of lenvatinib for patients with advanced hepatocellular carcinoma in a real-world setting. JGH Open 2019; 4: 54-60 |
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| Snippet | 症例は55歳女性．進行肝細胞癌に対してレンバチニブ8 mg/日の投与を開始した．投与開始時，疲労感はグレード0，血中アシルカルニチン/フリーカルニチン（AC/FC）比は0.158であった．投与8週目にグレード2の疲労感が出現し，AC/FC比は0.233に上昇した．レボカルニチン製剤1500... |
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| SubjectTerms | カルニチン バルプロ酸 レンバチニブ 疲労 肝細胞癌 |
| Title | レンバチニブ投与中の二峰性の疲労感に対してカルニチン補充療法が有用であった進行肝細胞癌の1例 |
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