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      Team Management of Skin Rash Associated with Use of Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitors

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          Abstract

          Objective:

          The aim of this study was to evaluate the effectiveness of a rash team management intervention designed by certified nurses, medical physicians, and certified pharmacists. The quality of life (QOL) of patients administered epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) was assessed using the dermatology life quality index (DLQI) and Skindex-29 QOL questionnaires.

          Methods:

          A total of 51 patients with nonsmall cell lung cancer who were treated using EGFR-TKIs were examined between November 1, 2014, and October 31, 2015, at the Institute of Biomedical Research and Innovation in Kobe city, Japan. All the patients were treated daily with erlotinib, gefitinib, or afatinib. The common terminology criteria for adverse events (version 4.0) system were used to grade treatment-induced toxicity events. The multimodality rash management team included nurses, pharmacists, and physicians. The team intervened before the initiation of treatment with EGFR-TKIs and at every visit. Patient QOL characteristics were evaluated using the DLQI and Skindex-29 assessment tools.

          Results:

          The number of patients with high-grade toxicity decreased when the multimodal approach was used. No grade 3 skin toxicities were recorded in the postintervention cohort. QOL scores for symptoms and feelings (emotions) were impaired in patients who were treated with EGFR-TKIs.

          Conclusions:

          The rash team management approach may be useful for patients treated with EGFR-TKIs. Specific QOL evaluation tools for the assessment of the effects of a team approach for rash management should be developed.

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          Most cited references15

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          Clinical and biological features associated with epidermal growth factor receptor gene mutations in lung cancers.

          Mutations in the tyrosine kinase (TK) domain of the epidermal growth factor receptor (EGFR) gene in lung cancers are associated with increased sensitivity of these cancers to drugs that inhibit EGFR kinase activity. However, the role of such mutations in the pathogenesis of lung cancers is unclear. We sequenced exons 18-21 of the EGFR TK domain from genomic DNA isolated from 617 non-small-cell lung cancers (NSCLCs) and 524 normal lung tissue samples from the same patients and 36 neuroendocrine lung tumors collected from patients in Japan, Taiwan, the United States, and Australia and from 243 other epithelial cancers. Mutation status was compared with clinicopathologic features and with the presence of mutations in KRAS, a gene in the EGFR signaling pathway that is also frequently mutated in lung cancers. All statistical tests were two sided. We detected a total of 134 EGFR TK domain mutations in 130 (21%) of the 617 NSCLCs but not in any of the other carcinomas, nor in nonmalignant lung tissue from the same patients. In NSCLC patients, EGFR TK domain mutations were statistically significantly more frequent in never smokers than ever smokers (51% versus 10%), in adenocarcinomas versus cancer of other histologies (40% versus 3%), in patients of East Asian ethnicity versus other ethnicities (30% versus 8%), and in females versus males (42% versus 14%; all P < .001). EGFR TK domain mutation status was not associated with patient age at diagnosis, clinical stage, the presence of bronchioloalveolar histologic features, or overall survival. The EGFR TK domain mutations we detected were of three common types: in-frame deletions in exon 19, single missense mutations in exon 21, and in-frame duplications/insertions in exon 20. Rare missense mutations were also detected in exons 18, 20, and 21. KRAS gene mutations were present in 50 (8%) of the 617 NSCLCs but not in any tumors with an EGFR TK domain mutation. Mutations in either the EGFR TK domain or the KRAS gene can lead to lung cancer pathogenesis. EGFR TK domain mutations are the first molecular change known to occur specifically in never smokers.
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            Epidermal growth factor receptor inhibitor-associated cutaneous toxicities: an evolving paradigm in clinical management.

            Epidermal growth factor receptor inhibitors (EGFRIs) have demonstrated improved overall survival in patients with non-small cell lung cancer, pancreatic cancer, and colorectal cancer; however, their use is associated with dermatologic reactions of varying severity. The similar spectrum of events observed with monoclonal antibodies and tyrosine kinase inhibitors suggests such toxicities are a class effect. While such reactions do not necessarily require any alteration in EGFRI treatment, being best addressed through symptomatic treatment, there is limited evidence on which to base such therapies. In October 2006, at an international and interdisciplinary EGFRI dermatologic toxicity forum, the underlying mechanisms of these toxicities were discussed and commonly used therapeutic interventions were evaluated. Our aim was to reach a current consensus on management strategies. A three-tiered, EGFRI-focused toxicity grading system is suggested for the purposes of therapeutic decision making, and as a framework on which to build a stepwise approach to intervention. This approach to successful management is specifically tailored to accurately categorize dermatologic toxicity associated with EGFRIs, and can be easily applied by all health care professionals. The goal is to maximize quality of life in patients who are being treated with these agents--many of whom will be on these drugs for several months or even years.
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              The Skindex instruments to measure the effects of skin disease on quality of life.

              Skindex-29 and Skindex-16 are validated measures of the effects of skin diseases on patients' quality of life. This article reviews the development of both versions of Skindex, discusses their measurement properties and interpretability, and gives examples of how they have been used and adapted for dermatologic research internationally. Studies of quality of life in patients with nonmelanoma skin cancer are described to illustrate the use of Skindex to understand quality of life and to compare effectiveness of different treatments for this highly prevalent condition.
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                Author and article information

                Journal
                Asia Pac J Oncol Nurs
                Asia Pac J Oncol Nurs
                APJON
                Asia-Pacific Journal of Oncology Nursing
                Medknow Publications & Media Pvt Ltd (India )
                2347-5625
                2349-6673
                Oct-Dec 2018
                : 5
                : 4
                : 430-434
                Affiliations
                [1 ]Department of Pathology and Molecular Diagnostics, Aichi Cancer Center, Nagoya, Japan
                [2 ]Division of Integrated Oncology, Institute of Biomedical Research and Innovation, Kobe, Japan
                [3 ]Nursing Department, Institute of Biomedical Research and Innovation, Kobe, Japan
                [4 ]Division of Pharmacy, Institute of Biomedical Research and Innovation, Kobe, Japan
                Author notes
                Corresponding author: Katsuhiro Masago, Department of Pathology and Molecular Diagnostics, Aichi Cancer Center, Nagoya, Japan Tel: +81-52-762-6111; Fax: +81-52-757-4810 E-mail: masago@ 123456aichi-cc.jp
                Article
                APJON-5-430
                10.4103/apjon.apjon_33_18
                6103195
                9f124607-10c5-440f-805e-c20cf73a8f9b
                Copyright: © 2018 Ann & Joshua Medical Publishing Co. Ltd

                This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms.

                History
                : 29 May 2018
                : 21 June 2018
                Categories
                Original Article

                epidermal growth factor receptor,skin toxicity,team management,tyrosine kinase inhibitor

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