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

A Cohort Study of Hand-Foot Skin Reaction in Patients with Unresectable Hepatocellular Carcinoma: Difference in the Occurrence in Hands and Feet

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.