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      The incidence and management of cutaneous adverse events of the epidermal growth factor receptor inhibitors

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          Abstract

          Overexpression of the epidermal growth factor receptor (EGFR) is found in many cancers, including those of the head and neck area, non-small-cell lung cancer, and colorectal, cervical, prostate, breast, ovary, stomach, and pancreatic cancer. The EGFR inhibitors are used at present in the treatment of such cancers. Skin lesions that develop during and after cancer treatment may be due to specific cytostatics, molecular-targeted drugs, radiation therapy, complementary therapy, or the cancer itself, and hence knowledge is essential to distinguish between them. The mechanism through which skin toxicity arises during treatment with EGFR inhibitors is not well known, but seems to be due to the modification of the RAS/RAF/MEK/ERK signal path associated with its activation, which results in the similarity between the adverse effects of EGFR inhibitors and the treatment of melanoma with BRAF and MEK inhibitors. The most common side effects are pruritus, xerosis, papulopustular rash, hand-foot skin reaction, alopecia and dystrophy of the hair, and paronychia. This work presents options for prevention and suggestions for managing these adverse events, which are of importance in the care of patients undergoing oncological treatment.

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          Most cited references44

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          Mechanisms of cutaneous toxicities to EGFR inhibitors.

          The increased target specificity of epidermal growth factor receptor (EGFR) inhibitors (EGFRIs) is associated with the reduction or abolition of nonspecific and haematopoietic side effects. However, coincident inhibition of receptor activity in tissues that depend on EGFR signalling for normal function has undesirable consequences. Because of the key role of EGFR signalling in skin, dermatological toxicities have frequently been described with EGFRIs. The resultant significant physical and psycho-social discomfort might lead to interruption or dose modification of anticancer agents. There is an urgent need for an improved understanding of these toxicities to develop adequate staging systems and mechanistically driven therapies, and to ensure quality of life and consistent antineoplastic therapy.
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            Third-generation inhibitors targeting EGFR T790M mutation in advanced non-small cell lung cancer

            The tyrosine kinase inhibitors (TKI) against epidermal growth factor receptor (EGFR) are widely used in patients with non-small cell lung cancer (NSCLC). However, EGFR T790M mutation leads to resistance to most clinically available EGFR TKIs. Third-generation EGFR TKIs against the T790M mutation have been in active clinical development. These agents include osimertinib, rociletinib, HM61713, ASP8273, EGF816, and PF-06747775. Osimertinib and rociletinib have shown clinical efficacy in phase I/II trials in patients who had acquired resistance to first- or second-generation TKIs. Osimertinib (AZD9291, TAGRISSO) was recently approved by FDA for metastatic EGFR T790M mutation-positive NSCLC. HM61713, ASP8237, EGF816, and PF-06747775 are still in early clinical development. This article reviews the emerging data regarding third-generation agents against EGFR T790M mutation in the treatment of patients with advanced NSCLC.
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              Cutaneous adverse effects of targeted therapies: Part I: Inhibitors of the cellular membrane.

              There has been a rapid emergence of numerous targeted agents in the oncology community in the last decade. This exciting paradigm shift in drug development lends promise for the future of individualized medicine. Given the pace of development and clinical deployment of targeted agents with novel mechanisms of action, dermatology providers may not be familiar with the full spectrum of associated skin-related toxicities. Cutaneous adverse effects are among the most frequently observed toxicities with many targeted agents, and their intensity can be dose-limiting or lead to therapy discontinuation. In light of the often life-saving nature of emerging oncotherapeutics, it is critical that dermatologists both understand the mechanisms and recognize clinical signs and symptoms of such toxicities in order to provide effective clinical management. Part I of this continuing medical education article will review in detail the potential skin-related adverse sequelae, the frequency of occurrence, and the implications associated with on- and off-target cutaneous toxicities of inhibitors acting at the cell membrane level, chiefly inhibitors of epidermal growth factor receptor, KIT, and BCR-ABL, angiogenesis, and multikinase inhibitors.
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                Author and article information

                Journal
                Postepy Dermatol Alergol
                Postepy Dermatol Alergol
                PDIA
                Advances in Dermatology and Allergology/Postȩpy Dermatologii i Alergologii
                Termedia Publishing House
                1642-395X
                2299-0046
                31 October 2017
                October 2017
                : 34
                : 5
                : 418-428
                Affiliations
                [1 ]Department of Dermatology, Military Institute of Medicine, Warsaw, Poland
                [2 ]Department of Dermatology, Pediatric Dermatology and Oncological Dermatology, Medical University of Lodz, Bieganski Hospital, Lodz, Poland
                [3 ]Department of Chemotherapy, Comprehensive Cancer Center and Traumatology, Copernicus Memorial Hospital, Lodz, Poland
                [4 ]Chair of Dermatology, Sexually Transmitted Diseases and Immunodermatology, Nicolaus Copernicus University in Torun, Faculty of Medicine in Bydgoszcz, Poland
                Author notes
                Address for correspondance: Witold Owczarek, Department of Dermatology, Military Institute of Medicine, 128 Szaserów St, 04-141 Warsaw, Poland, phone: +48 601 316 460, fax: +48 508 337 708. e-mail: witold.owczarek@ 123456dermedicus.pl
                Article
                30899
                10.5114/ada.2017.71106
                5831275
                29507555
                7c25743d-25c6-45d1-a90b-9cca5e839eaf
                Copyright: © 2017 Termedia Sp. z o. o.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0) License, allowing third parties to copy and redistribute the material in any medium or format and to remix, transform, and build upon the material, provided the original work is properly cited and states its license.

                History
                : 08 June 2016
                : 27 June 2016
                Categories
                Review Paper

                egfr inhibitor,dermatological adverse effects,braf inhibitor,mek inhibitor

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