Regorafenib-associated hand–foot skin reaction: practical advice on diagnosis, prevention, and management

Abstract

Regorafenib is an oral multikinase inhibitor licensed for use in gastrointestinal cancers. In clinical trials, regorafenib showed a consistent toxicity profile, including clinically significant hand–foot skin reaction (HFSR). Treatment modifications and symptomatic measures, as recommended in this review, can be used to manage HFSR and help patients to continue treatment at an optimal dose.

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

“…Without PDGFR signaling, tumor vessels destabilize and regress, resulting in tumor hypoxia [10]. Other receptor tyrosine kinases responsible for oncogenesis are v-kit Hardy-Zuckerman 4 feline sarcoma (c-KIT), rearranged during transfection (RET), rapidly accelerated fibrosarcoma (RAF)-1, and v-raf murine sarcoma viral oncogene homolog B (BRAF) [11]. Stem cell receptors are crucial for hematopoiesis and melanocyte differentiation.…”

Novel anti-angiogenic therapeutic strategies in colorectal cancer

“…The main limiting toxicities are fatigue and hand-foot skin reactions, which needed appropriate treatments [30].…”

Effectiveness of Topical Steroid Therapy for Prevention of Regorafenib associated Hand-foot Skin Reaction

“…The underlying mechanisms how Tyrosine Kinase Inhibitors (TKIs) cause HFSR remain unclear, but are suspected to be related to combined inhibition of several receptors such as vascular endothelial growth factor receptors and platelet-derived growth factor receptors [4]. Although HFSR is also caused by other TKIs, such as Sorafenib, Sunitinib, Axitinib, Pazopanib and Lenvatinib, the incidence rate of Regorafenib-induced HFSR seems to be higher than that of other TKIs especially for a Japanese population.…”

“…HFSR associated with TKIs occurs earlier compared with cytotoxic anticancer agents (fluoropyrimidines or taxanes). Patients with TKIs-associated HFSR often present with erythema, swelling, bullae, and hyperkeratosis, especially in pressure-bearing skin surface such as plams or soles [3][4][5][6][7][8][9][10][11]. Although there are no established therapeutic options available for TKIs-associated HFSR, it has recommended that pressure bearing should be avoided in daily life [4].…”

“…Patients with TKIs-associated HFSR often present with erythema, swelling, bullae, and hyperkeratosis, especially in pressure-bearing skin surface such as plams or soles [3][4][5][6][7][8][9][10][11]. Although there are no established therapeutic options available for TKIs-associated HFSR, it has recommended that pressure bearing should be avoided in daily life [4]. Maintaining moisture in affected skin surface is crucial, and prophylactic use of a urea-based cream is recommended in TKIs therapy [12,13].…”