Wollenberg A, Kroth J, Hauschild A, et al. Skin toxicity is generally manageable with standard topical or systemic antibiotics and anti-inflammatory agents. Ann Oncol 16(9):1425-33 (2005 Sep). This disease manifests as acute-onset dyspnea, usually occurring over a 24- to 48-hour period. Target Oncol 4(2):107-19 (2009 Apr). 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. Patients treated with EGFR inhibitors very likely develop cutaneous side effects. The rates of grade 3/4 hematologic side effects were generally similar in patients receiving chemotherapy alone and those also receiving cetuximab,3 and hematologic side effects are generally not significant with EGFR inhibitors. GIOTRIF ® (afatinib) has a well-characterised side effects profile 1-5. Severe diarrhea occurred in about 3% to 6% of the patients taking erlotinib, cetuximab, or gefitinib in phase III trials. Sign in While there is a general effect on symptom control and survival in some studies, limited subgroups of patients particularly benefit from this treatment. Infusion reactions have been seen with cetuximab, which is a monoclonal antibody with some murine properties. Perifollicular xanthomas associated with epidermal growth factor receptor inhibitor therapy. - Full-Length Features Li T, Perez-Soler R. Skin toxicities associated with epidermal growth factor receptor inhibitors. The small molecule kinase inhibitors often block multiple enzymes meaning means there is some cross over in the actions and side effects of these drugs. CT of the chest is often diagnostic and shows an inflammatory process within the lungs. Ocvirk J, Rebersek M. Managing cutaneous side effects with K1 vitamin creme reduces cutaneous toxicities induced by cetuximab. Cutaneous side-effects in cancer patients treated with the antiepidermal growth factor receptor antibody C225. Chung KY, Shia J, Kemeny NE, et al. J Dermatol Sci 42(2):91-9 (2006 May). EGFR inhibitors are associated with a unique group of class- specific cutaneous toxicities, which include acneiform eruptions, paronychia, xerosis, hyperpigmentation, trichomegaly, and telangiectasia. Clinical studies have shown that metformin and EGFR-TKI have synergistic effects in … URL: https: ... the most notable side effect being a maculopapular, acneiform rash in patients who respond (108). Potthoff K, Hofheinz R, Hassel JC, et al. Randomized double-blind trial of prophylactic oral minocycline and topical tazarotene for cetuximab-associated acne-like eruption. Write CSS OR LESS and hit save. It tends to be associated with dry skin and at times can be diffuse and very disruptive to activities of daily living. The higher expression of EGFR in the outer root sheath of the hair follicles may be causative for this infrequent but characteristic side-effect.4,8,12 Hyperpigmentation may appear after several months of EGFR inhibitor therapy. Segaert S, Tabernero J, Chosidow O, et al. A phase I and pharmacokinetic study of oral lapatinib administered once or twice daily in patients with solid malignancies. Don’t miss out on today’s top content on Oncology Nurse Advisor. J Eur Acad Dermatol Venereol 24(8):958-60 (2010 Aug). Anti-inflammatory activity of tetracyclines. This material may not be published, broadcast, rewritten or redistributed in any form without prior authorization. Patients in the cetuximab arm showed a 2-month improvement in overall survival. Appearance of more severe rash has been correlated with better treatment outcomes. Ann Oncol [Epub ahead of print] (2010 Aug 13). Burtness B, Goldwasser MA, Flood W, et al. Dermatology 211(4):330-3 (2005). All rights reserved. The most commonly seen toxicity from EGFR inhibitors is a papulopustular rash that erupts most often on the face but can also be seen on the chest, back, trunk, and limbs (Figure 1). The EGFR is physiologically expressed in epithelial tissues and hair follicles, where it contributes to epidermal proliferation, differentiation, and hair growth. View chapter Purchase book. Microbiological analysis of epidermal growth factor receptor inhibitor therapy-associated paronychia. 30 patients, acneiform eruptions were reduced significantly by the topical use of a cream containing urea and 0.1% K1 vitamin (Reconval K1®).26, Oral tetracyclines have been used for the treatment of acne vulgaris for more than 50 years27 because of their anti- inflammatory and immunomodulatory properties.28-30 These broad-spectrum polyketide antibiotics reduce neutrophilic chemotaxis and inhibit the production of proinflammatory cytokines and matrix metalloproteinase 9.29 Some recent studies investigated the benefit of prophylactic tetracycline for EGFR- induced acneiform eruptions.31-32 Tetracycline-treated patients reported less itching, burning, stinging, and other subjective symptoms compared with placebo. Histopathological analysis showed a neutrophilic suppurative infiltrate in the dermis, particularly involving the follicular infundibula. Dermato-oncologists are using oral isotretinoin more frequently, compared with oncologists, and are delaying EGFR inhibitor treatment less frequently because of skin toxicities.33 An interdisciplinary approach in cooperation with dermatologists is highly recommended to improve patient treatment.8,33, EGFR inhibitor-induced paronychia is seen in about 10% to 15% of all treated patients and may be quite painful, adversely affecting their quality of life.12 It generally does not develop during the first 6 weeks of treatment. 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. Oncogene 19(56):6550-65 (2000 Dec 27). Other less common GI side effects can be nausea and vomiting, anorexia, and stomatitis. Here, we demonstrate the first report of dual EGFR and ABL TKI treatment in a patient with concomitant EGFR-mutated lung adenocarcinoma and BCR-ABL1-positive chronic myeloid leukemia (CML). 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. Warm compresses for goopy, crusty morning eyes. These novel drugs are composed of an EGFR ligand or EGFR-binding antibody and a cytotoxic agent. PDF of CE 0810HOW TO TAKE THE POST-TEST: To obtain CE credit, please click here after reading the article to take the post-test on myCME.com. They occur in about 25% of patients and are characterized by pain, severe tenderness, and poor healing tendency.4,8 Fissures are challenging to treat. Use favorite eye drops as much as possible. Modest increases in plasma substance P (SP) occurred at 3 (+27%) and 9 (+25%) weeks. TCM combining EGFR-TKI administration illustrated no additional side effects for NSCLC patients According to the statistical analysis data of adverse effects in the Experimental group and Control group, there were no significant differences in rashes, diarrhea, ALT/AST increase, dental ulcer, or onychia lateralis between the 2 groups ( Table 2 , all p >0.05). The sebaceous glands are usually not affected. Grade 3/4 rash occurred in 9% of patients, and grade 3/4 diarrhea developed in 6% of patients.2. Hand-foot syndrome (HFS) induced by EGFR-TKI is rare. J Pharmacol Exp Ther 315(3):971-9 (2005 Dec). 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. We present an overview of the various cutaneous side-effects associated with EGFR inhibition and discuss their respective therapeutic options. Cunningham D, Humblet Y, Siena S, et al. Your use of this website constitutes acceptance of Haymarket Media’s Privacy Policy and Terms & Conditions. These drugs target receptors either on the outside of cancer cells or at an intracellular domain to inhibit cell survival, metastases, angiogenesis, and inhibition of apoptosis. Key Words: 4,8, Painful fissures on the tips of fingers and toes, on the nailfolds, and especially over the interphalangeal joints may develop as a consequence of excessively dry skin. Cetuximab (Erbitux) is another EGFR inhibitor. Wollenberg A, Moosmann N, Kroth J, et al. The rash commonly manifests in the first 1 to 2 weeks of treatment. here. Although these eruptions are considered a class effect from EGFR inhibition, antibody-induced eruptions tend to be more severe than TK1 induced skin changes.4, The pathogenesis of acneiform eruptions caused by EGFR is not yet fully understood. Rash is one of the most common toxicities in patients treated with EGFR inhibitors. The most common localisation of the skin side ef-fects of the TKI EGFR therapy is the head and trunk area. EGFR inhibitors can often shrink tumors for several months or more. Certain drugs, herbal supplements and even foods can affect the way TKIs work in the body. side-effects from EGFR Tyrosine Kinase Inhibitors in Lung Cancer Derriford Hospital Derriford Road Plymouth PL6 8DH Tel: 01752 202082 www.plymouthhospitals.nhs.uk . Hu JC, Sadeghi P, Pinter-Brown LC, et al. Erlotinib is a small molecule. Osimertinib (Tagrisso) TKI EGFR inhibitor ... (CML) and the cardiovascular side effects have been extensively reviewed by Moslehi et al. Clinical practice guidelines for the prevention and treatment of EGFR inhibitor-associated dermatologic toxicities Supportive Care in Cancer, Volume 19, Number 8, 1079-1095, DOI: 10.1007/s00520-011-1197-6. Painful aphthae and larger erosions may appear on the oral mucosa, lips, and nose, as well as on the anal and genital mucosa. The rate of grade 3/4 infusion reactions with cetuximab was about 4% in the lung cancer trial.3 Some electrolyte imbalances, such as hypomagnesemia and hypokalemia, have been more common in patients taking cetuximab and are often exacerbated by diarrhea. The follicles are frequently enlarged and sometimes obstructed by excess keratinocytes. Enjoying our content? You may report side effects to FDA at 1-800-FDA-1088. Burris HA, 3rd, Taylor CW, Jones SF, et al. A 60-year-old man with an 8-year history of CML was diagno… 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. © SkinTherapyLetter. Localized measures that are pain-relieving and soothing will provide considerable symptomatic relief. Allergo J 15:559-65 (2006). But eventually these drugs stop working for most people, usually because the cancer cells develop another mutation in the EGFR gene. 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. 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 N Engl J Med 351(4):337-45 (2004 Jul 22). Drug Saf 14(6):375-85 (1996 Jun). Evidence-based practice for the unique side effects associated with EGFR inhibitors is still evolving. Results for the adverse event profile in the LUX-LUNG 3 study that resulted in the approval of afatinib in non-small-cell lung cancer (NSCLC) showed that 89% of patients treated with the agent developed rash, with 16% having rash that was grade 3 or higher (JCO 2013, 31:3327–… Receptor ( EGFR ) inhibitors are an increasingly important treatment option for cancer... Ef-Fects of the TKI EGFR therapy is the head and trunk area usually because the cells! Receptor targeted therapies less common late phase reactions from therapy with EGFR inhibitors very likely cutaneous!, usually because the cancer cells develop another mutation in the United States 42... Of patient selection and novel strategies these drugs receptor family as targets for cancer therapy clinical presentation, pathogenesis and. Benefit with a more amenable side effect articles this month the oncology Nurse Advisor perineal regions treatment.... 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