Yoshida Yu, Sasaoka Sayaka, Tanaka Mizuki, Matsumoto Kiyoka, Inoue Misaki, Satake Riko, Shimada Kazuyo, Mukai Ririka, Suzuki Takaaki, Iwata Mari, Goto Fumiya, Mori Takayuki, Mori Koki, Yoshimura Tomoaki, Nakamura Mitsuhiro
Laboratory of Drug Informatics, Gifu Pharmaceutical University, Gifu, Japan.
Department of Pharmacy, Ogaki Municipal Hospital, Ogaki, Japan.
Ther Adv Drug Saf. 2022 May 24;13:20420986221101963. doi: 10.1177/20420986221101963. eCollection 2022.
The aim of our study was to assess the clinical features of hand-foot syndrome (HFS) associated with certain systemic chemotherapeutic drugs in a real-world setting using the Japanese Adverse Drug Event Report (JADER) database.
HFS was defined using the preferred terms from the Medical Dictionary for Regulatory Activities. We used several indices, such as the reporting odds ratios (RORs) at 95% confidence interval (CI), the time-to-onset profile of HFS, and cluster analysis.
Of 646,779 reports (submission period: April 2004 to September 2020), 1814 reported HFS events. The RORs (95% CI) for axitinib, capecitabine, lapatinib, regorafenib, sorafenib, and sunitinib were 14.9 (11.1-20.1), 54.6 (49.2-60.6), 130.4 (110.7-153.6), 63.3 (55.2-72.6), 29.0 (25.8-32.7), and 13.9 (11.7-16.5), respectively. The analysis of time-to-onset profiles revealed that the median values (interquartile range: 25.0-75.0%) of drug-induced HFS caused by capecitabine, cisplatin, docetaxel, everolimus, regorafenib, sorafenib, and trastuzumab were 21.0 (13.0-42.0), 15.0 (10.0-82.0), 6.0 (3.0-25.0), 86.5 (67.0-90.5), 9.0 (6.0-14.0), 9.0 (6.0-14.0), and 70.0 (15.0-189.0) days, respectively. The number of clusters was set to 4. Among these, one cluster, which included capecitabine, regorafenib, and lapatinib, exhibited a higher reporting ratio and ROR of drug-induced HFS than other drugs.
The RORs and results of time-to-onset analysis obtained in this study indicated the potential risk of HFS associated with chemotherapeutic drugs. Our results suggest that health care professionals must be aware of the potential onset of drug-induced HFS with docetaxel, regorafenib, and sorafenib for at least 4 weeks; therefore, careful observation is recommended.
Hand-foot syndrome (HFS) is an adverse effect of some cancer drugs, which is characterized by symptoms such as redness, swelling, blistering, and pain in the area of palms and soles. HFS reduces the quality of life of patients and can sometimes interfere with anticancer treatment plans. It is important to understand the clinical manifestations of HFS and gain knowledge that will allow for early intervention by clinicians. In this study, we used a large-scale side effect database of real-world cases for a comprehensive investigation of anticancer-drug-induced HFS. The database contained 646,779 adverse event reports from April 2004 to September 2020; among which, we identified 1814 HFS events. Using these data, we could obtain information on the relationship between 19 types of anticancer drugs and HFS, and the onset time of HFS and HFS prognosis related to each anticancer drug. Our results suggest that clinicians should monitor the risk of HFS with docetaxel, regorafenib, and sorafenib for at least the first 4 weeks after drug administration. These findings are crucial for improving the management of the adverse effects caused by anticancer drugs.
我们研究的目的是利用日本药品不良反应报告（JADER）数据库，在真实世界环境中评估与某些全身化疗药物相关的手足综合征（HFS）的临床特征。
使用《药物监管活动医学词典》中的首选术语来定义HFS。我们使用了几个指标，如95%置信区间（CI）的报告比值比（ROR）、HFS的发病时间概况和聚类分析。
在646,779份报告（提交时间段：2004年4月至2020年9月）中，有1814份报告了HFS事件。阿昔替尼、卡培他滨、拉帕替尼、瑞戈非尼、索拉非尼和舒尼替尼的ROR（95%CI）分别为14.9（11.1 - 20.1）、54.6（49.2 - 60.6）、130.4（110.7 - 153.6）、63.3（55.2 - 72.6）、29.0（25.8 - 32.7）和13.9（11.7 - 16.5）。对发病时间概况的分析显示，由卡培他滨、顺铂、多西他赛、依维莫司、瑞戈非尼、索拉非尼和曲妥珠单抗引起的药物性HFS的中位数（四分位间距：25.0 - 75.0%）分别为21.0（13.0 - 42.0）、15.0（10.0 - 82.0）、6.0（3.0 - 25.0）、86.5（67.0 - 90.5）、9.0（6.0 - 14.0）、9.0（6.0 - 14.0）和70.0（15.0 - 189.0）天。聚类数设定为4。其中，一个包含卡培他滨、瑞戈非尼和拉帕替尼的聚类显示，与其他药物相比，药物性HFS的报告率和ROR更高。
本研究获得的ROR和发病时间分析结果表明了与化疗药物相关的HFS的潜在风险。我们的结果表明，医护人员必须意识到多西他赛、瑞戈非尼和索拉非尼引起的药物性HFS至少在4周内有潜在发病风险；因此，建议进行仔细观察。
手足综合征（HFS）是某些抗癌药物的一种不良反应，其特征是手掌和脚底部位出现发红、肿胀、水疱和疼痛等症状。HFS会降低患者的生活质量，有时还会干扰抗癌治疗计划。了解HFS的临床表现并获取能让临床医生进行早期干预的知识很重要。在本研究中，我们使用了一个大规模的真实世界病例副作用数据库，对抗癌药物引起的HFS进行全面调查。该数据库包含2004年4月至2020年9月的646,779份不良事件报告；其中，我们识别出1814例HFS事件。利用这些数据，我们可以获得19种抗癌药物与HFS之间的关系、HFS的发病时间以及与每种抗癌药物相关的HFS预后信息。我们的结果表明，临床医生应在给药后的至少前4周监测多西他赛、瑞戈非尼和索拉非尼引起HFS的风险。这些发现对于改善抗癌药物引起的不良反应的管理至关重要。
