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A 58-year-old man developed abrupt, intensely painful plantar erythema with desquamation 10–11 days after starting donafenib, progressing rapidly to CTCAE grade 3 HFSR. Donafenib was immediately stopped with short-term symptomatic care, followed by a successful switch to lenvatinib, which was well tolerated without high-grade skin toxicity recurrence. The case emphasizes early detection, accurate grading, timely interruption, and mechanism-informed switching based on differing toxicity profiles.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/donafenib-intolerance-in-hepatocellular-carcinoma-severe-hand-foot-skin-reaction-and-successful-switch-to-lenvatinib-a-case-report-and-literature-review/410209/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/donafenib-intolerance-in-hepatocellular-carcinoma-severe-hand-foot-skin-reaction-and-successful-switch-to-lenvatinib-a-case-report-and-literature-review/410209.png","ImageObject",300,407,{"name":92,"@type":93},"Margaret","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-30","2026-09-28",true,{"@type":102,"interactionType":103,"userInteractionCount":39},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What complication is reported after starting donafenib in hepatocellular carcinoma?","Question",{"text":112,"@type":113},"The case reports severe hand-foot skin reaction (HFSR) with intensely painful plantar erythema and desquamation developing shortly after donafenib initiation.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How was the severe HFSR managed and what was the immediate treatment step?",{"text":117,"@type":113},"Donafenib was immediately discontinued and short-term symptomatic management was provided, leading to prompt improvement of acral lesions.",{"name":119,"@type":110,"acceptedAnswer":120},"Why was switching to lenvatinib successful in this patient?",{"text":121,"@type":113},"After the switch, lenvatinib was well tolerated without recurrence of high-grade skin toxicity, supporting a mechanism-informed approach based on differing toxicity profiles between the drugs.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},410209,1790764577,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":39,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":39,"language":139,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":140,"faqs":141,"seo_title":142,"seo_description":67,"update_tm":143,"read_time":46,"preview_page_count":4},137451207643,"https://ap-avatar.wpscdn.com/davatar_3d24733baf745e90a7e4bdd5f77d97b2","TYPE Case Report  \nPUBLISHED 18 December 2025 DOI 10.3389/fonc.2025.1728098  \nOPEN ACCESS  \nEDITED BY  \nJonaid Ahmad Malik,  \nSchool of Medicine Southern Illinois University, United States  \nREVIEWED BY  \nMd. Rizwanullah,  \nJamia Hamdard University, India Mohammed Kaleem,  \nKing Abdulaziz University, Saudi Arabia Dr. Mohd Rihan,  \nUSF Health, United States Kartik Chandra Guchhait,  \nDebra Thana Sahid Kshudiram Smriti Mahavidyalaya, India  \nKhursheed Sheikh,  \nJamia Hamdard University, India  \n*CORRESPONDENCE  \nYinuo Tan  \n [tan0yi0nuo@zju.edu.cn](tan0yi0nuo@zju.edu.cn)[ ](tan0yi0nuo@zju.edu.cn)Yuqi Jin  \n[jinyuqidoctor@zju.edu.cn](jinyuqidoctor@zju.edu.cn)[ ](jinyuqidoctor@zju.edu.cn)†These authors share first authorship  \nRECEIVED 19 October 2025  \nREVISED 22 November 2025  \nACCEPTED 24 November 2025  \nPUBLISHED 18 December 2025  \nCITATION  \nChen Y, Fu L, Song P, Tan Y and Jin Y (2025) Donafenib intolerance in hepatocellular carcinoma: severe hand–foot skin reaction and successful switch to lenvatinib – a case report and literature review.  \nFront. Oncol. 15:1728098 .  \ndoi: 10.3389/fonc.2025.1728098  \nCOPYRIGHT  \n© 2025 Chen, Fu, Song, Tan and Jin. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.  \nDonafenib intolerance in hepatocellular carcinoma:  \nsevere hand–foot skin reaction and successful switch to lenvatinib – a case report and literature review  \nYing Chen 1†, Linglin Fu 2†, Ping Song 1, Yinuo Tan 3,4,5,6* and Yuqi Jin 3,4,5,6*  \n1 Department of Nursing, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China, 2School of Renji Medical Sciences, Wenzhou Medical University, Wenzhou, China, 3 Department of Medical Oncology, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China, 4Zhejiang Provincial Clinical Research Center for Cancer, Hangzhou, China, 5Cancer Center of Zhejiang University, Hangzhou, China, 6Center for Medical Research and Innovation in Digestive System Tumors, Ministry of Education, Hangzhou, China  \nBackground: Donafenib is an approved multikinase inhibitor for hepatocellular carcinoma (HCC) . However, cutaneous toxicity—particularly hand–foot skin reaction (HFSR)—may necessitate treatment interruption and compromise therapeutic continuity.  \nCase presentation: A 58-year-old man with HCC on a cirrhotic background developed abrupt onset of intensely painful plantar erythema with overlying desquamation 10–11 days after initiating donafenib. The lesions rapidly progressed, leading to impaired ambulation and were consistent with CTCAE grade 3 HFSR.  \nManagement and outcome: Donafenib was immediately discontinued, and the patient received short-term symptomatic management, resulting in prompt improvement of the acral lesions . He was subsequently transitioned tolenvatinib, which was well tolerated without recurrence of high-grade skin toxicity. The patient maintained clinical stability and was able to continue systemic anticancer therapy.  \nConclusion: This case highlights the importance of early detection and accurate grading of HFSR, timely treatment interruption, and mechanism-informed switching to an alternative tyrosine kinase inhibitor such as lenvatinib. It also underscores key differences in toxicity profiles between donafenib—associated with VEGFR/RAF-related cutaneous injury—and lenvatinib, which is more commonly linked to hypertension, diarrhea, and appetite or weight changes.  \nKEYWORDS  \ndonafenib, hepatocellular carcinoma, hand–foot skin react","cbCaiiMVtjctjiKh","https://ap.wps.com/l/cbCaiiMVtjctjiKh","pdf",1324273,"English","# Introduction\n## Donafenib and systemic therapy in HCC\n## MKI-related HFSR and practical management\n# Case presentation\n## Onset and severity of HFSR after donafenib\n# Management and outcome\n## Discontinuation, symptomatic care, and switch to lenvatinib\n# Conclusion","[{\"question\":\"What complication is reported after starting donafenib in hepatocellular carcinoma?\",\"answer\":\"The case reports severe hand-foot skin reaction (HFSR) with intensely painful plantar erythema and desquamation developing shortly after donafenib initiation.\"},{\"question\":\"How was the severe HFSR managed and what was the immediate treatment step?\",\"answer\":\"Donafenib was immediately discontinued and short-term symptomatic management was provided, leading to prompt improvement of acral lesions.\"},{\"question\":\"Why was switching to lenvatinib successful in this patient?\",\"answer\":\"After the switch, lenvatinib was well tolerated without recurrence of high-grade skin toxicity, supporting a mechanism-informed approach based on differing toxicity profiles between the drugs.\"}]","Donafenib intolerance in hepatocellular carcinoma - severe hand-foot skin reaction and successful switch to lenvatinib - a case report and literature review | PDF",1790584644]