Multikinase Inhibitor-Induced Hand–Foot Skin Reaction: A Review of Clinical Presentation, Pathogenesis, and Management

4008 Background: Sorafenib (SOR) has become the standard treatment for advanced hepatocellular carcinoma (HCC). Hand-foot skin reaction (HFSR) is one of the most common adverse events associated with SOR and its occurrence can impact patient quality of life and lead to dose modification or interruption, both of which may negatively impact clinical outcomes. This randomized controlled trial is the first large prospective study to investigate the prophylactic effect of urea-based creams on HFSR associated with SOR. Methods: Patients with advanced HCC treated with SOR were randomly assigned 1:1 to receive prophylactic urea-based cream (Arm A) or best supportive care (BSC) following development of HFSR (Arm B). SOR was administered 800 mg daily. Urea-based cream was given twice daily for up to 12 weeks starting on Day 1. BSC was at the physician’s discretion and excluded urea-based creams. The primary endpoint was the incidence of all-grade HFSR in the first12 weeks. Results: Eight hundred sixty eight patients were enrolled; 439 patients in Arm A and 432 patients in Arm B. There was no difference of baseline characteristics between two arms. Over the 12 week period of study, the incidence of all-grade HFSR was significantly lower in Arm A compared to Arm B; n=246 (56.0%) patients in Arm A versus n=318 (73.6%) patients in Arm B, p<0.0001. The incidence of grade ≥2 HFSR tended to be lower in Arm A compared to Arm B, but did not reach statistical significance; n=96 (21.9%) patients Arm A versus n=126 (29.2%) patients in Arm B, p=0.1638. The median time to the first HFSR event was 2.5 fold longer in Arm A compared to Arm B; 84 days (95% CI 45-93 days) in Arm A and 34 days (95% CI 29-43 days) in Arm B (p<0.001). Conclusions: This is the first large prospective, randomized control trial examining the prophylactic use of urea-based creams for treatment of HFSR associated with a multikinase inhibitor. Compared to BSC, prophylactic topical use of a urea-based cream appears to be effective in preventing and/or delaying the incidence of HFSR associated with SOR treatment in patients with advanced HCC.

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Treatment and prevention of hand-foot skin reaction — dermatological adverse effect of regorafenib (literature review)

Medical alphabet ◽

10.33667/2078-5631-2019-3-28(403)-57-61 ◽

2019 ◽

Vol 3 (28) ◽

pp. 57-61

Author(s):

E. A. Shatokhina ◽

L. S. Kruglova ◽

P. G. Nosikova

Keyword(s):

Adverse Event ◽

Skin Reaction ◽

Tumor Therapy ◽

Skin Toxicity ◽

Common Adverse Event ◽

Published Data ◽

Multikinase Inhibitor ◽

Treatment And Prevention ◽

Hand Foot Skin Reaction ◽

Unique Mechanism

Regorafenib is an agent of targeted cancer therapy, that is a multikinase inhibitor of angiogenesis, oncogenesis, microenvironment and tumor immune system. Due to the unique mechanism of action, regorafenib is highly effective in the treatment of various tumors. The most common adverse event associated with regorafenib, leading to a dose reduction or its cancellation, is a manifestation of skin toxicity — hand-foot skin reaction. The review compiles published data based on research and experience in managing this dermatological adverse event. Adequate staff and patient awareness, monitoring, prevention, and treatment are necessary to reduce the incidence, duration, and severity of hand-foot skin reaction associated with regorafenib. Determining the optimal management for patients with this complication becomes an essential component of the complex treatment of patients receiving regorafenib anti-tumor therapy, especially considering the fact that hand-foot skin reaction is a marker of its effectiveness.

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