Donafenib intolerance in hepatocellular carcinoma: severe hand-foot skin reaction and successful switch to lenvatinib - a case report and literature review.

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.