A novel approach to manage skin toxicity caused by therapeutic agents targeting epidermal growth factor receptor.

Abstract

636 Background: Inhibition of EGFR represents an important field in cancer therapy.Skin rash is a common adverse reaction in patients receiving EGFR inhibitors. Nicotinamide has been shown to be an effective treatment for skin inflammation in various conditions, since nicotinamide inhibits IL-8 production through the NF-kB and MAPK pathways in an in vitro keratinocytes/P. acnes model of inflammation. Furthermore green tea polyphenols could be useful in attenuation of solar UVB light-induced oxidative stress-mediated and MAPK-caused skin disorders in humans.In this study we evaluated the effect of nicotinamide and green tea polyphenols on skin toxicity EGFRI related. Methods: Patients with skin toxicity induced by EGFRI were enrolled. They underwent a skin biopsy and skin samples for microbiological analyses at first presentation of skin toxicity (T0). Skin toxicity was assessed with NCI-CTACE,EGFR index and Dermatology Life Quality Index (DLQI) test. Therapy protocol consisted in topical application of moisturizing cream containing green tea polyphenols plus oral administration of nicotinamide 200 mg/die for 12 weeks. Topical application of 1% clindamycin gel and/or systemic administration of minocicline were provided in case of superbacterial infection. All treated patients were monitored for at least 12 weeks (T12), across three time points (T0,T6,T12). Results: 24 colorectal cancer patients receiving anti-EGFR monoclonal antibodies (cetuximab or panitumumab) and developing skin toxicity were treated by a multidisciplinary team including oncologists, dermatologists, a pathologist and a nurse. All the patients experienced a significant reduction of skin toxicity according to the NCI-CTACE and EGFR index (p<0.05). Papulo-pustular eruption and itching significantly improved after 6 weeks of treatment and erythema decreased after 12 weeks. A significative improvement of the global score and of DLQI was evident. No toxicity related to the treatment of skin toxicity was observed. Conclusions: Treatment with nicotinamide and green tea polyphenols represent a novel effective approach to manage skin toxicity caused by EGFRI.