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      Effects of tyrosine kinase inhibitor therapy on skin toxicity and skin-related quality of life in patients with lung cancer : An observational study

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          Abstract

          Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) therapy is the primary treatment option for patients with non-small cell lung cancer (NSCLC). However, one of the major adverse effects associated with this therapy is skin toxicity, which impacts the patient's quality of life. This study aimed to describe the severities and locations of skin toxicity, and to analyze their association with the quality of life in patients with advanced NSCLC who received EGFR-TKI therapy as first-line treatment.

          This cross-sectional and correlation study was conducted at a tertiary medical center in northern Taiwan between July 2015 and March 2016. Skin toxicity was assessed and graded using the National Cancer Institute Common Terminology Criteria for Adverse Events (version 4.03). The Skindex-16 scale was used to measure the skin disease-related quality of life.

          A total of 146 NSCLC patients who received EGFR-TKI therapy within the first 3 months of diagnosis were included in this study; 93.2% of these patients experienced skin toxicities. Approximately 70% of the patients developed xerosis and pruritus, while 50% had papulopustular eruptions and paronychia. The mean skin symptom impact score was 5.38 (standard deviation = 2.65). The skin-related quality of life varied widely among the participants but remained acceptable (mean score = 13.96, standard deviation = 16.55). Skin symptoms correlated significantly with poor quality of life (r = 0.50, P < .001). Younger patients and those treated with afatinib were the most affected, reporting the poorest quality of life. Patients who required EGFR-TKI dose reduction had experienced more severe skin symptoms than had patients who did not require it (7.35 vs 5.01, P < .001).

          Skin toxicity related to EGFR-TKI treatment impacts the quality of life in patients with NSCLC. During the treatment period, skin assessment and tailored management should be incorporated into the daily care plan.

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          Most cited references20

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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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            Skin toxicity evaluation protocol with panitumumab (STEPP), a phase II, open-label, randomized trial evaluating the impact of a pre-Emptive Skin treatment regimen on skin toxicities and quality of life in patients with metastatic colorectal cancer.

            Panitumumab, a fully human monoclonal antibody targeting the epidermal growth factor receptor (EGFR), is approved in the United States and Europe for the treatment of refractory metastatic colorectal cancer (mCRC). Skin toxicities are the most common adverse events with EGFR inhibitors. This is the first study designed to examine differences between pre-emptive and reactive skin treatment for specific skin toxicities in patients with mCRC for any EGFR inhibitor. Patients receiving panitumumab-containing therapy were randomly assigned 1:1 to pre-emptive or reactive treatment (after skin toxicity developed). Pre-emptive treatment included use of skin moisturizers, sunscreen, topical steroid, and doxycycline. The primary end point of the study was the incidence of protocol-specified >or= grade 2 skin toxicities during the 6-week skin treatment period. Quality of life (QOL) was assessed with the Dermatology Life Quality Index (DLQI). Of 95 enrolled patients, 48 received pre-emptive treatment, and 47 received reactive treatment. The incidence of protocol-specified >or= grade 2 skin toxicities during the 6-week skin treatment period was 29% and 62% for the pre-emptive and reactive groups, respectively. Mean DLQI score change from baseline to week 3 was 1.3 points and 4.2 points in the pre-emptive and reactive groups, respectively. The pre-emptive skin treatment regimen was well tolerated. The incidence of specific >or= grade 2 skin toxicities during the 6-week skin treatment period was reduced by more than 50% in the pre-emptive group compared with the reactive group. Patients in the pre-emptive group reported less QOL impairment than patients in the reactive group.
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              Quality of life of patients with lung cancer

              Lung cancer is the major cause of oncologic-related death worldwide. Due to delayed diagnosis, 5-year survival rate accounts for only 15%. Treatment includes surgery, adjuvant chemotherapy, and radiation therapy; however, it is burdened by many side effects. Progress of the disease, severity of its symptoms, and side effects decrease significantly the quality of life (QoL) in those patients. The level of self-assessed QoL helps in predicting survival, which is especially important among patients receiving palliative care. Patients assess their functioning in five dimensions (physical, psychological, cognitive, social, and life roles), severity of symptoms, financial problems, and overall QoL. The QoL in lung cancer patients is lower than in healthy population and patients suffering from other malignancies. It is affected by the severity and the number of symptoms such as fatigue, loss of appetite, dyspnea, cough, pain, and blood in sputum, which are specific for lung tumors. Fatigue and respiratory problems reduce psychological dimension of QoL, while sleep problems reduce cognitive functioning. Physical dimension (related to growing disability) decreases in most of the patients. Also, most of them are unable to play their family and social roles. The disease is a frequent reason of irritation, distress, and depression. Management of the disease symptoms may improve QoL. Controlling the level of fatigue, pulmonary rehabilitation, and social and spiritual support are recommended. Early introduction of tailored palliative treatment is a strategy of choice for improvement of QoL in lung cancer patients.
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                Author and article information

                Journal
                Medicine (Baltimore)
                Medicine (Baltimore)
                MEDI
                Medicine
                Wolters Kluwer Health
                0025-7974
                1536-5964
                05 June 2020
                05 June 2020
                : 99
                : 23
                : e20510
                Affiliations
                [a ]Department of Nursing, Chang Gung Memorial Hospital (Linkuo)
                [b ]School of Nursing, College of Medicine, Chang Gung University
                [c ]Division of Pulmonary Oncology and Interventional Bronchoscopy, Department of Thoracic Medicine
                [d ]Department of General Surgery, Chang Gung Memorial Hospital (Linkuo), Taoyuan, Taiwan.
                Author notes
                []Correspondence: Li-Chueh Weng, School of Nursing, College of Medicine, Chang Gung University, Department of General Surgery, Chang Gung Memorial Hospital Linkuo, Taiwan (e-mail: ax2488@ 123456mail.cgu.edu.tw ).
                Author information
                http://orcid.org/0000-0002-6926-988X
                Article
                MD-D-19-05477 20510
                10.1097/MD.0000000000020510
                7306373
                32501998
                d6d64e44-44bb-4c77-852e-87ed7ed9c5aa
                Copyright © 2020 the Author(s). Published by Wolters Kluwer Health, Inc.

                This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0

                History
                : 11 July 2019
                : 23 November 2019
                : 27 April 2020
                Categories
                5700
                Research Article
                Observational Study
                Custom metadata
                TRUE

                advanced non-small cell lung cancer,dermatological side effects,quality of life,skin toxicity,targeted therapy

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