Strategies for Prevention and Treatment of Chemotherapy-Induced Hand-Foot- Skin-Reaction (HFSR)

Abstract

DescriptionHand-foot-skin-reaction (HFSR), also known as palmoplantar erythrodysesthesia, is a frequently occurring side effect of many antineoplastic therapies. Interruption, dose reduction or even discontinuation of anti-tumor therapy due to missing strategies in prevention or treatment of HFSR can be the consequence. According to severity grade of HFSR restrictions in activities of daily life can occur, which can lead to an impairment of quality of life (QOL). Especially skin-related QOL, which actually can be assessed by a variety of different questionnaires, often decreases when HFSR occurs, which can be underlined by some lately published investigations. Nardone and coworkers used the skindex-16 questionnaire to measure the skin-related QOL of patients treated with sunitinib and sorafenib. Patients with higher grades of HFSR showed lower results in the symptoms and emotions scores of the skindex-16 [1]. Chan et al. report in a lately published review that CTCAE grading of HFSR seems to correlate well with skin-related QOL, irrespective of the available questionnaires used for assessment [2].Main agents potentially causing HFSR are tyrosine kinase inhibitors such as sorafenib, sunitinib or regorafenib as well as cytostatic agents like pegylated liposomal doxorubicin (PLD), taxanes and pyrimidine analogues (infusional 5-Fluorouracil or capecitabine). The overall incidence rate of HFSR differs from 20% to 60%, depending on trialdesigns and analyzed anti-cancer drugs [3][4][5][6][7][8].The pathomechanism of HFSR actually seems not to be sufficiently explained. Almost 20 years ago the observed skin reaction in patients treated with a high-dosed chemotherapy led to one of the leading theories for development of HFSR [9]. According to this theory, toxic active metabolites resulting from the applied chemotherapy were eliminated over the eccrine sweat glands of the skin and caused severe damage. Especially at the palms of the hands and the planta of the feet as well as intertrigineous areas the count of sweat glands is highest in human body. Additionally, the thick stratum corneum of the skin in these areas serves as a reservoir for the toxic metabolites leading to severe skin reaction. Recently, other potential pathomechanism were suggested by Lademann and coworkers. New optical methods were used to detect fluorescent substances such as anthracyclines on the skin surface and around the sweat glands during or after administration [10]. As a consequence the excretion of toxic metabolites over the sweat glands results in formation of free radicals and hence in damaging cellular components. Thus, a prevention of HFSR using antioxidant agents seemed reasonable.PROCAPP, an open label randomized phase III trial was conducted to compare the prophylactic effect of Mapisal and urea-cream in patients receiving capecitabine therapy [11]. Mapisal is a medical device containing a huge variety of antioxidants and other nourishing ingredients. Patients with gastrointestinal or breast cancer not pretreated with tyrosine kinase inh...