切除不能な肝細胞がん患者を対象としたHand−Foot Skin Reaction(手足皮膚症候群)発生の実態—手と足の違いに着目して

要旨 切除不能な肝細胞がん治療に用いられるtyrosine kinase inhibitor(TKI)の副作用の1つにhand-foot skin reaction(HFSR)がある.本研究は手と足におけるHFSR発生率,HFSRの症状,発生時期を明らかにすることを目的とした. 本研究はコホート研究で,切除不能な肝細胞がんに対してレンバチニブ,ソラフェニブ,レゴラフェニブによる治療を受ける患者を対象に,2カ月間の診察日に問診と手足の写真撮影を行った.写真はフットケアエキスパートナースを含む3名で皮膚症状を確認した.手足それぞれのHFSR発生日をカプラン-マイヤー曲線を用いて描出し,log-ra...

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Published in日本がん看護学会誌 Vol. 37; no. 1; pp. 35 - 41
Main Authors 田原 裕希恵, 雨宮 歩, 加瀨 竜太郎, 北川 柚香, 小笠原 定久, 加藤 直也, 小宮山 政敏
Format Journal Article
LanguageJapanese
Published 日本がん看護学会 02.02.2023
一般社団法人 日本がん看護学会
Subjects
Online AccessGet full text
ISSN0914-6423
2189-7565
DOI10.18906/jjscn.37_35_tahara

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Abstract 要旨 切除不能な肝細胞がん治療に用いられるtyrosine kinase inhibitor(TKI)の副作用の1つにhand-foot skin reaction(HFSR)がある.本研究は手と足におけるHFSR発生率,HFSRの症状,発生時期を明らかにすることを目的とした. 本研究はコホート研究で,切除不能な肝細胞がんに対してレンバチニブ,ソラフェニブ,レゴラフェニブによる治療を受ける患者を対象に,2カ月間の診察日に問診と手足の写真撮影を行った.写真はフットケアエキスパートナースを含む3名で皮膚症状を確認した.手足それぞれのHFSR発生日をカプラン-マイヤー曲線を用いて描出し,log-rank検定を実施した.本研究は千葉大学大学院看護学研究科倫理審査委員会の承認を得て実施された. 研究に参加した58名のHFSR発生率は84%であり,最も多く観察された症状は角質剥離で,参加者の23%は手に,参加者の39%は足にみられた.HFSR発生日の中央値は,手が21日(95%信頼区間17.6〜24.3日),足が7日(95%信頼区間11.6〜14.3日)と,足のほうが早くHFSRが発生していた(log-rank検定,p<0.01). 本研究結果から,HFSRの早期発見には手だけではなく足の観察も重要であると考えられた.看護師はTKI治療開始前から診察日ごとに患者の手足を観察することで軽微な変化も見逃さず,適切な治療につなげる役割が期待される.  Hand-foot skin reaction (HFSR) is one adverse event that can occur following the use of tyrosine kinase inhibitor (TKI) for unresectable hepatocellular carcinoma. The HFSR incidence in each of the hands and feet is unclear. Therefore, the purpose of this study was to compare the incidence, symptoms, and time of HFSR occurrence between the hands and feet. This study aimed to provide evidence to support patients treated using TKI. A cohort study was conducted with the approval of the Ethical Review Committee of the Graduate School of Nursing, Chiba University including patients to be treated with lenvatinib, sorafenib, and regorafenib for unresectable hepatocellular carcinoma. The patients were tracked for 2 months, and the skin symptoms on their hands and feet were surveyed. During the entire study period, the patients were asked about their subjective symptoms, and photographs of their hands and feet were taken at each hospital visit. Photographs of the hands and feet were checked for skin symptoms by three people, including a footcare expert nurse. The date of HFSR occurrence in each hand and foot was described using the Kaplan-Meier curve and analyzed using the log-rank test. The HFSR incidence was 84% out of 58 patients who provided consent to this study conducted between September 2018 and March 2020. The most common symptom was skin peeling of the hands and feet, which was observed in 23% and 39% of patients, respectively. The median HFSR occurrence dates were 21 days for the hands (95% CI 17.6-24.3 days) and 13 days for the feet (95% CI 11.6-14.3 days), indicating that the feet had earlier HFSR (log-rank test p < 0.01). This study indicated that observation of patients' feet as well as hands is important for early detection of HFSR. Nurses are expected to check the patient's hands and feet from before the start of TKI treatment and then during every hospital visit, so that even small skin changes are not missed and patients are supported to receive appropriate treatment.
AbstractList 切除不能な肝細胞がん治療に用いられるtyrosine kinase inhibitor(TKI)の副作用の1つにhand-foot skin reaction(HFSR)がある.本研究は手と足におけるHFSR発生率,HFSRの症状,発生時期を明らかにすることを目的とした.本研究はコホート研究で,切除不能な肝細胞がんに対してレンバチニブ,ソラフェニブ,レゴラフェニブによる治療を受ける患者を対象に,2カ月間の診察日に問診と手足の写真撮影を行った.写真はフットケアエキスパートナースを含む3名で皮膚症状を確認した.手足それぞれのHFSR発生日をカプラン-マイヤー曲線を用いて描出し,log-rank検定を実施した.本研究は千葉大学大学院看護学研究科倫理審査委員会の承認を得て実施された.研究に参加した58名のHFSR発生率は84%であり,最も多く観察された症状は角質剥離で,参加者の23%は手に,参加者の39%は足にみられた.HFSR発生日の中央値は,手が21日(95%信頼区間 17.6〜24.3日),足が7日(95%信頼区間 11.6〜14.3日)と,足のほうが早くHFSRが発生していた(log-rank検定, p<0.01).本研究結果から,HFSRの早期発見には手だけではなく足の観察も重要であると考えられた.看護師はTKI治療開始前から診察日ごとに患者の手足を観察することで軽微な変化も見逃さず,適切な治療につなげる役割が期待される.
要旨 切除不能な肝細胞がん治療に用いられるtyrosine kinase inhibitor(TKI)の副作用の1つにhand-foot skin reaction(HFSR)がある.本研究は手と足におけるHFSR発生率,HFSRの症状,発生時期を明らかにすることを目的とした. 本研究はコホート研究で,切除不能な肝細胞がんに対してレンバチニブ,ソラフェニブ,レゴラフェニブによる治療を受ける患者を対象に,2カ月間の診察日に問診と手足の写真撮影を行った.写真はフットケアエキスパートナースを含む3名で皮膚症状を確認した.手足それぞれのHFSR発生日をカプラン-マイヤー曲線を用いて描出し,log-rank検定を実施した.本研究は千葉大学大学院看護学研究科倫理審査委員会の承認を得て実施された. 研究に参加した58名のHFSR発生率は84%であり,最も多く観察された症状は角質剥離で,参加者の23%は手に,参加者の39%は足にみられた.HFSR発生日の中央値は,手が21日(95%信頼区間17.6〜24.3日),足が7日(95%信頼区間11.6〜14.3日)と,足のほうが早くHFSRが発生していた(log-rank検定,p<0.01). 本研究結果から,HFSRの早期発見には手だけではなく足の観察も重要であると考えられた.看護師はTKI治療開始前から診察日ごとに患者の手足を観察することで軽微な変化も見逃さず,適切な治療につなげる役割が期待される.  Hand-foot skin reaction (HFSR) is one adverse event that can occur following the use of tyrosine kinase inhibitor (TKI) for unresectable hepatocellular carcinoma. The HFSR incidence in each of the hands and feet is unclear. Therefore, the purpose of this study was to compare the incidence, symptoms, and time of HFSR occurrence between the hands and feet. This study aimed to provide evidence to support patients treated using TKI. A cohort study was conducted with the approval of the Ethical Review Committee of the Graduate School of Nursing, Chiba University including patients to be treated with lenvatinib, sorafenib, and regorafenib for unresectable hepatocellular carcinoma. The patients were tracked for 2 months, and the skin symptoms on their hands and feet were surveyed. During the entire study period, the patients were asked about their subjective symptoms, and photographs of their hands and feet were taken at each hospital visit. Photographs of the hands and feet were checked for skin symptoms by three people, including a footcare expert nurse. The date of HFSR occurrence in each hand and foot was described using the Kaplan-Meier curve and analyzed using the log-rank test. The HFSR incidence was 84% out of 58 patients who provided consent to this study conducted between September 2018 and March 2020. The most common symptom was skin peeling of the hands and feet, which was observed in 23% and 39% of patients, respectively. The median HFSR occurrence dates were 21 days for the hands (95% CI 17.6-24.3 days) and 13 days for the feet (95% CI 11.6-14.3 days), indicating that the feet had earlier HFSR (log-rank test p < 0.01). This study indicated that observation of patients' feet as well as hands is important for early detection of HFSR. Nurses are expected to check the patient's hands and feet from before the start of TKI treatment and then during every hospital visit, so that even small skin changes are not missed and patients are supported to receive appropriate treatment.
Author 加藤 直也
北川 柚香
雨宮 歩
加瀨 竜太郎
小宮山 政敏
田原 裕希恵
小笠原 定久
AuthorAffiliation 千葉大学大学院医学研究院 消化器内科学
千葉大学大学院看護学研究院 健康増進看護学講座
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References 6) Kaneko S, Ikeda K, Matsuzaki Y, et al. Safety and effectiveness of sorafenib in Japanese patients with hepatocellular carcinoma in daily medical practice: interim analysis of a prospective postmarketing all-patient surveillance study. Journal of Gastroenterology. 51 (10), 1011-1021 (2016
2) エーザイ株式会社. レンバチニブメシル酸塩, 医薬品医療機器総合機構. 2019-12. https://www.info.pmda.go.jp/go/pack/4291039M1020_1_18/ (参照2020-9-29
12) 日本腫瘍研究グループ. 有害事象共通用語規準 v5.0日本語訳JCOG版, Japan Clinical Oncology Group. 2017-3-10. http://www.jcog.jp/doctor/tool/index3.html (参照2020-9-19
19) 山本有紀. マルチキナーゼ阻害剤による皮膚障害. Monthly Book Derma. (264), 62-66 (2017
8) Chu D, Lacouture ME, Weinerc E, et al. Risk of hand-foot skin reaction with the multitargeted kinase inhibitor sunitinib in patients with renal cell and non-renal cell carcinoma: a meta-analysis. Clinical Genitourinary Cancer. 7 (1), 11-19 (2009
10) 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. 391 (10126), 1163-1173 (2018
13) Urakawa R, Tarutani M, Kubota K, et al. Hand foot syndrome has the strongest impact on QOL in skin toxicities of chemotherapy. Journal of Cancer. 10 (20), 4846-4851 (2019
3) バイエル薬品株式会社. ソラフェニブトシル酸塩, 医薬品医療機器総合機構. 2019-11 https://www.info.pmda.go.jp/go/pack/4291029F1028_1_10/ (参照2020-9-29
14) Lacouture ME, Wu S, Robert C, et al. Evolving strategies for the management of hand-foot skin reaction associated with the multitargeted kinase inhibitors sorafenib and sunitinib. The Oncologist. 13 (9), 1001-1011 (2008
1) 厚生労働省 大臣官房統計情報部 人口動態・保健社会統計課保健統計室. 平成26年 (2014) 患者調査の概況, 厚生労働省. https://www.mhlw.go.jp/toukei/saikin/hw/kanja/14/ (参照 2020-9-29
18) 文部科学省, 厚生労働省. 人を対象とする医学系研究に関する倫理指針 平成29年2月28日一部改定, 厚生労働省. 2017-2-28. http://www.mhlw.go.jp/file/06-Seisakujouhou-10600000-Daijinkanboukouseikagakuka/0000153339.pdf (参照2020-9-29
11) Lee WJ, Lee JL, Chang SE, et al. Cutaneous adverse effects in patients treated with the multitargeted kinase inhibitors sorafenib and sunitinib. The British Journal of Dermatology. 161 (5), 1045-1051 (2009
7) Yoshino T, Komatsu Y, Yamada Y, et al. Randomized phase III trial of regorafenib in metastatic colorectal cancer: Analysis of the CORRECT Japanese and non-Japanese subpopulations. Investigational New Drugs. 33 (3), 740-750 (2015
16) 森本悦子, 井上菜穂美, カペシタビンによる手足症候群予防のための看護支援の現状 —全国のがん化学療法看護認定看護師に対する実態調査より. 日本がん看護学会誌, 28 (1), 30-36 (2014
5) Yamashita T, Kudo M, Ikeda K, et al. REflECT — a phase 3 trial comparing efficacy and safety of lenvatinib to sorafenib for the treatment of unresectable hepatocellular carcinoma: an analysis of Japanese subset. Journal of Gastroenterology. 55 (1), 113-122 (2020
17) McLellan B, Ciardiello F, Lacouture ME, et al. Regorafenib-associated hand-foot skin reaction: practical advice on diagnosis, prevention, and management. Annals of Oncology. 26, 2017-2026 (2015
4) バイエル薬品株式会社. レゴラフェニブ水和物, 医薬品医療機器総合機構. 2019-9. https://www.info.pmda.go.jp/go/pack/4291017F1025_1_26/ (参照2020-9-29
15) Sibaud V, Delord J, Chevreau C. Sorafenib-induced hand-foot skin reaction: A Koebner phenomenon? Targeted Oncology. 4, 307-310 (2009
9) Belum VR, Wu S, Lacouture ME. Risk of hand-foot skin reaction with the novel multikinase inhibitor regorafenib: a meta-analysis. Investigational New Drugs. 31, 1078-1086 (2013
References_xml – reference: 19) 山本有紀. マルチキナーゼ阻害剤による皮膚障害. Monthly Book Derma. (264), 62-66 (2017)
– reference: 12) 日本腫瘍研究グループ. 有害事象共通用語規準 v5.0日本語訳JCOG版, Japan Clinical Oncology Group. 2017-3-10. http://www.jcog.jp/doctor/tool/index3.html (参照2020-9-19)
– reference: 7) Yoshino T, Komatsu Y, Yamada Y, et al. Randomized phase III trial of regorafenib in metastatic colorectal cancer: Analysis of the CORRECT Japanese and non-Japanese subpopulations. Investigational New Drugs. 33 (3), 740-750 (2015)
– reference: 1) 厚生労働省 大臣官房統計情報部 人口動態・保健社会統計課保健統計室. 平成26年 (2014) 患者調査の概況, 厚生労働省. https://www.mhlw.go.jp/toukei/saikin/hw/kanja/14/ (参照 2020-9-29)
– reference: 4) バイエル薬品株式会社. レゴラフェニブ水和物, 医薬品医療機器総合機構. 2019-9. https://www.info.pmda.go.jp/go/pack/4291017F1025_1_26/ (参照2020-9-29)
– reference: 15) Sibaud V, Delord J, Chevreau C. Sorafenib-induced hand-foot skin reaction: A Koebner phenomenon? Targeted Oncology. 4, 307-310 (2009)
– reference: 5) Yamashita T, Kudo M, Ikeda K, et al. REflECT — a phase 3 trial comparing efficacy and safety of lenvatinib to sorafenib for the treatment of unresectable hepatocellular carcinoma: an analysis of Japanese subset. Journal of Gastroenterology. 55 (1), 113-122 (2020)
– reference: 11) Lee WJ, Lee JL, Chang SE, et al. Cutaneous adverse effects in patients treated with the multitargeted kinase inhibitors sorafenib and sunitinib. The British Journal of Dermatology. 161 (5), 1045-1051 (2009)
– reference: 14) Lacouture ME, Wu S, Robert C, et al. Evolving strategies for the management of hand-foot skin reaction associated with the multitargeted kinase inhibitors sorafenib and sunitinib. The Oncologist. 13 (9), 1001-1011 (2008)
– reference: 18) 文部科学省, 厚生労働省. 人を対象とする医学系研究に関する倫理指針 平成29年2月28日一部改定, 厚生労働省. 2017-2-28. http://www.mhlw.go.jp/file/06-Seisakujouhou-10600000-Daijinkanboukouseikagakuka/0000153339.pdf (参照2020-9-29)
– reference: 3) バイエル薬品株式会社. ソラフェニブトシル酸塩, 医薬品医療機器総合機構. 2019-11 https://www.info.pmda.go.jp/go/pack/4291029F1028_1_10/ (参照2020-9-29)
– reference: 9) Belum VR, Wu S, Lacouture ME. Risk of hand-foot skin reaction with the novel multikinase inhibitor regorafenib: a meta-analysis. Investigational New Drugs. 31, 1078-1086 (2013)
– reference: 8) Chu D, Lacouture ME, Weinerc E, et al. Risk of hand-foot skin reaction with the multitargeted kinase inhibitor sunitinib in patients with renal cell and non-renal cell carcinoma: a meta-analysis. Clinical Genitourinary Cancer. 7 (1), 11-19 (2009)
– reference: 16) 森本悦子, 井上菜穂美, カペシタビンによる手足症候群予防のための看護支援の現状 —全国のがん化学療法看護認定看護師に対する実態調査より. 日本がん看護学会誌, 28 (1), 30-36 (2014)
– reference: 10) 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. 391 (10126), 1163-1173 (2018)
– reference: 17) McLellan B, Ciardiello F, Lacouture ME, et al. Regorafenib-associated hand-foot skin reaction: practical advice on diagnosis, prevention, and management. Annals of Oncology. 26, 2017-2026 (2015)
– reference: 6) Kaneko S, Ikeda K, Matsuzaki Y, et al. Safety and effectiveness of sorafenib in Japanese patients with hepatocellular carcinoma in daily medical practice: interim analysis of a prospective postmarketing all-patient surveillance study. Journal of Gastroenterology. 51 (10), 1011-1021 (2016)
– reference: 2) エーザイ株式会社. レンバチニブメシル酸塩, 医薬品医療機器総合機構. 2019-12. https://www.info.pmda.go.jp/go/pack/4291039M1020_1_18/ (参照2020-9-29)
– reference: 13) Urakawa R, Tarutani M, Kubota K, et al. Hand foot syndrome has the strongest impact on QOL in skin toxicities of chemotherapy. Journal of Cancer. 10 (20), 4846-4851 (2019)
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Snippet 要旨 切除不能な肝細胞がん治療に用いられるtyrosine kinase inhibitor(TKI)の副作用の1つにhand-foot skin reaction(HFSR)がある.本研究は手と足におけるHFSR発生...
切除不能な肝細胞がん治療に用いられるtyrosine kinase inhibitor(TKI)の副作用の1つにhand-foot skin reaction(HFSR)がある.本研究は手と足におけるHFSR発生...
SourceID jstage
igakushoin
SourceType Publisher
StartPage 35
SubjectTerms hand-foot skin reaction
time of occurrence
tyrosine kinase inhibitor
チロシンキナーゼ阻害薬
手足皮膚症候群
発生時期
Title 切除不能な肝細胞がん患者を対象としたHand−Foot Skin Reaction(手足皮膚症候群)発生の実態—手と足の違いに着目して
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https://www.jstage.jst.go.jp/article/jjscn/37/0/37_37_35_tahara/_article/-char/ja
Volume 37
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ispartofPNX 日本がん看護学会誌, 2023/02/02, Vol.37, pp.37_35_tahara
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