CASE REPORT article
Front. Oncol.
Sec. Pharmacology of Anti-Cancer Drugs
This article is part of the Research TopicDrug Repurposing: The New Frontier in Fighting CancerView all articles
Donafenib intolerance in hepatocellular carcinoma: severe hand–foot skin reaction and successful switch to lenvatinib – a case report and literature review
Provisionally accepted
- 1Zhejiang University, Hangzhou, China
- 2The Second Affiliated Hospital Zhejiang University School of Medicine, Hangzhou, China
- 3Wenzhou Medical University, Wenzhou, China
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Background: 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. Case 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. Management 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 to lenvatinib, which was well tolerated without recurrence of high-grade skin toxicity. The patient maintained clinical stability and was able to continue systemic anticancer therapy. Conclusion: 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.
Keywords: Donafenib, Hepatocellular Carcinoma, hand–foot skin reaction, acral toxicity, Lenvatinib, tyrosine kinase inhibitor, Multikinase inhibitor, case report
Received: 19 Oct 2025; Accepted: 24 Nov 2025.
Copyright: © 2025 Tan, Chen, Fu 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) or licensor 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.
* Correspondence:
Yinuo Tan, tan0yi0nuo@zju.edu.cn
Yuqi Jin, jinyuqidoctor@zju.edu.cn
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