Hand-Foot Syndrome (Hand-Foot Skin Reaction, Palmar-Plantar Erythrodysesthesia): Focus on Sorafenib and Sunitinib

Abstract

Hand-foot syndrome (HFS), also called hand-foot skin reaction, palmar-plantar erythrodysesthesia, acral erythema, and Burgdorf reaction, is a dose-limiting cutaneous toxicity of many chemotherapeutic agents. Recently, the multiple tyrosine kinase inhibitor class of novel targeted therapies, including sorafenib and sunitinib, has emerged as an important cause of HFS, with 10–28% of patients treated with sunitinib and 10–62% of patients treated with sorafenib reporting HFS. This review examines the epidemiology, clinical features, histopathology, pathogenesis models, prognostic implications, and management of HFS, with particular attention to HFS induced by sorafenib and sunitinib. The high prevalence of HFS reported by patients treated with these medications underscores the need for greater understanding of the pathogenesis and management of this syndrome.

The Adverse Effects of Sorafenib in Patients with Advanced Cancers

“…The syndrome of HFSR usually occurs 2-4 weeks after the initiation of sorafenib therapy, with the median onset of 18.4 days. Notably, the TKI-induced HFSR has the distinct feature of larger affected areas such as interphalangeal joints, palms, soles and hyperkeratotic lesions surrounded by erythematous areas [59].…”

“…The incidence of HFSR was even higher in the patients with DTC, as indicated by the phase III DECISION study for radioactive iodine refractory DTC [10]. The pathogenesis of HFSR has been evaluated and several risk factors were identified, such as gender (female), malignant types (RCC or non-RCC) and exposure dosage [56,[59][60][61]. The proposed risk factors for HFSR include impaired kidney function and decreased glomerular filtration rate (GFR), which were associated with systemic overexposure of sorafenib [62].…”

Differentiating hand-foot syndrome from tinea in patients receiving chemotherapy

“…Although the pathogenesis of this cutaneous side effect is still poorly understood, proposed mechanisms include capillary damage leading to drug extravasation and, especially in the case of liposomal doxorubicin, drug accrual in the eccrine sweat ducts of the hands and feet [11]. The typical clinical presentation of HFS includes a prodromal paresthesia followed by painful, symmetrical erythema, scale, and edema of the palms and soles that may evolve into blisters and fissures [11,12].…”

A Case Report on Capecitabine Induced Hand Foot Syndrome and Mucositis

“…5-Fluorouracil (5FU) and its oral prodrug Capecitabine, Cytarabine, Doxorubicin, Epirubicin, Fluorode oxyuridine, Hydroxyurea, Mercaptopurine, Cyclophosphamide, Docetaxel and tyrosine kinase inhibitors including Sorafenib and Sunitinib are the frequently involved agents causing HFS. 1,2 Capecitabine with the advantage of oral administration is currently indicated for treatment of Colorectal cancer, Breast cancer and advanced Upper Gastrointestinal cancer. 3 HFS is a well defined adverse effect of Capecitabine; others being nausea, vomiting, oral mucositis, diarrhea and myelosuppression.…”