Li T, Perez-Soler R. Skin toxicities associated with epidermal growth factor receptor inhibitors. J Am Acad Dermatol 56(2):317-26 (2007 Feb). Infusion reactions have been seen with cetuximab, which is a monoclonal antibody with some murine properties. Gefitinib (Iressa) was the first EGFR inhibitor to become available in the United States. Gutzmer R, Werfel T, Kapp A, et al. The management of skin reactions in cancer patients receiving epidermal growth factor receptor targeted therapies. receiving EGFR TKI therapy rarely demonstrate T790M resistance mutations, which is consistent with a pharmacological rather than biological mechanism [44,45]. The discovery of EGFR mutations in the tyrosine kinase domain may present the possibility of patient selection and novel strategies. J Clin Oncol 23(34):8646-54 (2005 Dec 1). A phase I and pharmacokinetic study of oral lapatinib administered once or twice daily in patients with solid malignancies. Vallbohmer D, Lenz HJ. Calculated antibiotic treatment of paronychia is recommended with oral cephalosporines, but oral fluoroquinolones may also be used, especially if Gram-negative infection is suspected. Appearance of more severe rash has been correlated with better treatment outcomes. Our first choice for severe acneiform eruptions is early treatment with a combination of low dose oral retinoid, topical nadifloxacin, and topical prednicarbate.21-22 We limit the use of this highly effective “triple therapy” to the first 2-3 months of EGFR- inhibitor treatment.21 Some authors have raised the issue of increased xerosis or reduced anticancer properties of the EGFR- inhibitors, 5,10,11 whereas others see a potential synergistic effect of this combinatorial approach.11, Management of acneiform skin eruptions is influenced by the level of dermatological background of the treating physician.33 Microbiological analysis of epidermal growth factor receptor inhibitor therapy-associated paronychia. Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. side-effects from EGFR Tyrosine Kinase Inhibitors in Lung Cancer Derriford Hospital Derriford Road Plymouth PL6 8DH Tel: 01752 202082 www.plymouthhospitals.nhs.uk . It tends to be associated with dry skin and at times can be diffuse and very disruptive to activities of daily living. It is import to educate patients about these side-effects, in order to increase compliance. 1 st line EGFR M+ ... EGFR M+ TKI Sequence Effectiveness: Final Analysis Dose Modification & Effectiveness Uncommon EGFR pooled analysis Resources ... India; Home > Safety > Side Effects. EGFR inhibitors are associated with a unique group of class- specific cutaneous toxicities, which include acneiform eruptions, paronychia, xerosis, hyperpigmentation, trichomegaly, and telangiectasia. The present study describes, for the first time, HFS induced by high-dose icotinib in a 65- … Download this brochure for patients suffering with EGFRI side effects. CT of the chest is often diagnostic and shows an inflammatory process within the lungs. Dermatology 211(4):330-3 (2005). Topical therapy with nadifloxacin cream and prednicarbate cream improves acneiform eruptions caused by the EGFR-inhibitor cetuximab – A report of 29 patients. This side effect can be very bothersome, given the resultant itching, fissuring with associated pain, or even bacterial or rarely herpes simplex virus super infection . Switching EGFR-TKIs because of adverse events provided a clinical benefit for patients with EGFR mutation-positive NSCLC. J Eur Acad Dermatol Venereol 24(8):958-60 (2010 Aug). It is not yet FDA approved for NSCLC, but it does have a Medicare compendia approval and clinical trial data to support its use in metastatic NSCLC. [Therapy of severe cetuximab-induced acneiform eruptions with oral retinoid, topical antibiotic and topical corticosteroid]. Busam KJ, Capodieci P, Motzer R, et al. The characteristic distribution pattern is similar to that of acne vulgaris, but there are no comedones present. Perifollicular xanthomas associated with epidermal growth factor receptor inhibitor therapy. Pathologe 27(1):53-6 (2006 Feb). Wollenberg A, Kroth J, Hauschild A, et al. Certain drugs, herbal supplements and even foods can affect the way TKIs work in the body. We present an overview of the various cutaneous side-effects associated with EGFR inhibition and discuss their respective therapeutic options. The most common localisation of the skin side ef-fects of the TKI EGFR therapy is the head and trunk area. Enjoying our content? During the first few weeks of treatment, acneiform eruptions are the earliest common side-effect. Copyright © 2020 Haymarket Media, Inc. All Rights Reserved Drug Saf 14(6):375-85 (1996 Jun). Some patients may also experience dryness of vaginal and perineal regions. Patients in the cetuximab arm showed a 2-month improvement in overall survival. Thus, concurrent use of an EGFR TKI with chemotherapy in the first-line setting remains investigational. tyrosine kinase inhibitors (TKI) (eg, erlotinib, gefitinib): these bind to the tyrosine kinase domain in the epidermal growth factor receptor and stop the activity of the EGFR monoclonal antibodies (eg, cetuximab, necitumumab): these bind to the extracellular component of the EGFR and prevent epidermal growth factor from binding to its own receptor, therefore preventing cell division. Fingernail involvement may lead to significant functional impairment. EGFR inhibitor-induced urticarial and anaphylactoid reactions are frequently seen in the US, but these are rarely encountered in Europe.9-10 Here, we review the diagnostic procedures and current treatment options for the more common side-effects of EGFR inhibitors.4,8,11-16, Acneiform eruptions are the earliest and most characteristic side-effect of EGFR inhibition. Patients treated with EGFR inhibitors very likely develop cutaneous side effects. The development of a papulopustular, follicular exanthema during the first weeks of therapy correlates with therapeutic benefit. Don’t miss out on today’s top content on Oncology Nurse Advisor. Daily online exclusives cover late breaking oncology news, safe handling and administration of chemotherapy drugs, side effect management, and new developments in specific cancers. Grade 3/4 rash occurred in 9% of patients, and grade 3/4 diarrhea developed in 6% of patients.2. Treatment of acne vulgaris with tetracycline hydrochloride: a double-blind trial with 51 patients. These telangiectasias vanish with time, but often leave some degree of hyperpigmentation.4,12. It provides a clinical score with five grades of severity.4 The dermatological skin score (WoMoScore) is a sensitive dermatologic scoring system for the long-term assessment of acneiform skin rashes that has been used in our department since 2006.22 The final WoMoScore is calculated from body involvement, facial involvement, and clinical grading of erythema, papulation, postulation, scaling, and crusts, providing a clinical score ranging from 0 to 100.22 Mild skin changes score up to 20, moderate cases range between 20 and 40, whereas severe acneiform eruptions exceed a WoMoScore of 40.20, Treatment of mild acneiform eruptions mostly involves Targeted therapies have been a large part of the advances—in particular, one class of drugs called epidermal growth factor receptor (EGFR) inhibitors. Drugs of this type have a different structure and work at different places in the cell than large molecule drugs; they are typically able to diffuse into cells and can act on targets that are found inside the cell. In addition to the pivotal role of EGFR in the development and progression of malignant tumors, EGFR is also important for proliferation and differentiation of the human epidermis and hair follicles. - Evidence-Based Guidance Cetuximab shows activity in colorectal cancer patients with tumors that do not express the epidermal growth factor receptor by immunohistochemistry. Adverse effects reported previously with TKI use, include fatigue, ... "If we identify longer-term side effects with TKIs then we might want to think about ... mean eGFR … It is given once daily at a recommended dose of 150 mg. Based on the results of a large, randomized, phase III clinical trial showing improved response rates and overall survival in patients taking erlotinib versus placebo, erlotinib was FDA approved for second- or third-line treatment of locally advanced or metastatic NSCLC after failure of a prior chemotherapy regimen.2 The most common side effects experienced by patients in the study were rash and diarrhea. Diarrhea is another common class effect of these drugs. However, the median progression-free survival (PFS) of NSCLC patients treated with EGFR-TKI is only 10–12 months, so the problem of drug resistance in treatment needs to be urgently solved. This material may not be published, broadcast, rewritten or redistributed in any form without prior authorization. ILD is an acute inflammation of lung tissue as a reaction to the drug and is a reason for permanent discontinuation of therapy. Burris HA, 3rd, Taylor CW, Jones SF, et al. Nonspecific … You’ve viewed {{metering-count}} of {{metering-total}} articles this month. Icotinib is a new oral epidermal growth factor tyrosine kinase inhibitor (EGFR-TKI). It gained Medicare approval for use as a result of a large, randomized, phase III clinical trial commonly known as the FLEX trial.3 This predominantly European trial randomized chemotherapy-naive patients with stage IIIB/IV lung cancer to receive first-line cisplatin and vinorelbine (CV) or CV plus cetuximab. However, prophylactic tetracyclines did not lower the total incidence of the rash.31-32, Tetracyclines are clearly effective, but they may lead to unwanted systemic effects that are not encountered with topical treatment. Appropriate judgment regarding switching from one EGFR-TKI to another may improve the performance status and prognosis of patients with EGFR mutation-positive NSCLC. Systemic treatment of paronychia is recommended for all painful or infected lesions, as there is a risk for the development of erysipelas, deep panaritium, and tendon sheath phlegmon. Patients frequently present with involvement of the great toenails. In studies of gefitinib, ILD occurred in 0.3% to 1% of the US population and in about 2% of Japanese patients.5 ILD rates in the BR.21 erlotinib trial were less than 1%.2, From the August 01, 2010 Issue of Oncology Nurse Advisor, Already have an account? Liquid cyanoacrylate glue may be tried for recurrent cases.4,8, Trichomegaly, with or without additional hypertrichosis, may develop after 2 to 5 months of continuous anti-EGFR treatment. Laura Maximiliane Ehmann, MD, Thomas Ruzicka, MD and Andreas Wollenberg, MD 3 Imatinib, a first generation TKI was followed by the second generation TKIs nilotinib, dasatinib and bosutinib and the third-generation agent ponatinib. Side effects of TKI EGFR are observed in the majority of patients (Table 6); however, unlike the toxicity of chemotherapy they are rarely life threatening. Almost all side-effects are temporary and will resolve several weeks after discontinuation of EGFR inhibitor therapy. You may report side effects to FDA at 1-800-FDA-1088. At the start of your treatment your doctor will ask about your normal Nicotinamide: An Update and Review of Safety & Differences from Niacin, Update on Drugs & Devices: November – December 2020, The Therapeutic Potential of Cannabinoids in Dermatology, Vitamin B Derivative (Nicotinamide) Appears to Reduce Skin Cancer Risk, Imiquimod 5% Cream (Aldara®) in the Treatment of Basal Cell Carcinoma, Sirolimus: A Therapeutic Advance for Dermatologic Disease, Non-Invasive Gene Expression Testing to Rule Out Melanoma, Management of Non-melanoma Skin Cancers in Canada. Fissures are less common late phase reactions from therapy with EGFR inhibitors. Toxicity of EGFR TKI The toxicity profile of different EGFR TKIs is quite similar and focuses on skin dryness, acneiform rash, asthenia and diarrhoea; fatal but rare risk of pulmonary toxicity requires cautious administration of these drugs in patients with predisposing diseases (pulmonary fibrosis) and in … Table 1 provides information on incidence and severity. Clin Cancer Res 15(21):6702-8 (2009 Nov 1). Consequently, the prophylactic use of sunscreens is highly recommended to prevent these solar-induced reactions. A tool for scoring of acneiform skin eruptions induced by EGF receptor inhibition. Murata K, Sugita K, Kobayashi M, et al. Patients must be warned to stay out of the sun, because photosensitivit y is increased during therapy with EGFR inhibitors and quite severe acneiform reactions can be triggered by UV exposure. The incidence may be as high as 75% to 100% of cases.2,4,8,14,16-19 Evidence suggests that severity of the skin rash might be a surrogate marker determining clinical outcome of patients receiving EGFR inhibitor treatment.1,19-21 The eruption usually occurs after 1 week of treatment. Cetuximab is a monoclonal antibody that attaches to the EGFR receptor on the cell surface (large molecule), thus preventing binding of the EGF ligand to the receptor. Onkologie 33(3):94-8 (2010). Phase III randomized trial of cisplatin plus placebo compared with cisplatin plus cetuximab in metastatic/recurrent head and neck cancer: an Eastern Cooperative Oncology Group study. All of the TKIs list keratitis (irritation to the cornea) as a side effect. Many EGFR inhibitors are given orally and present new challenges for oncology nurses, pharmacists, and physicians. 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