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. Fissures are less common late phase reactions from therapy with EGFR inhibitors. Schafer-Korting M, Schmid MH, Korting HC. Webster G, Del Rosso JQ. Warm compresses for goopy, crusty morning eyes. Acta Derm Venereol 90(2):202-3 (2010 Mar). Infusion reactions have been seen with cetuximab, which is a monoclonal antibody with some murine properties. This material may not be published, broadcast, rewritten or redistributed in any form without prior authorization. As a consequence, cutaneous side-effects are frequently observed during cancer therapy with EGFR inhibitors. The most frequent side-effects of icotinib include rash and diarrhea. Interdisciplinary management of EGFR- inhibitor-induced skin reactions: a German expert opinion. Phase II trial of cetuximab in patients with refractory colorectal cancer that expresses the epidermal growth factor receptor. [Therapy of severe cetuximab-induced acneiform eruptions with oral retinoid, topical antibiotic and topical corticosteroid]. What Are Side Effects of Gilotrif? 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 These novel drugs are composed of an EGFR ligand or EGFR-binding antibody and a cytotoxic agent. In addition, EGFR is overexpressed in many solid tumors, where it is involved in tumor growth, cell proliferation, apoptosis, angiogenesis, cell motility, and metastasis.1 Preclinical and clinical studies have shown that inhibiting EGFR is a valid strategy in anticancer therapy.1,2. Thanks for visiting Oncology Nurse Advisor. 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. 18. Erlotinib is a small molecule. Some patients may also experience dryness of vaginal and perineal regions. Segaert S, Tabernero J, Chosidow O, et al. Consequently, the prophylactic use of sunscreens is highly recommended to prevent these solar-induced reactions. Li T, Perez-Soler R. Skin toxicities associated with epidermal growth factor receptor inhibitors. ... inhibitors, albeit at the cost of greater toxicity causing side effects including high-grade diarrhea, 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. Cetuximab (Erbitux) is another EGFR inhibitor. Treatment of acne vulgaris with tetracycline hydrochloride: a double-blind trial with 51 patients. 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 . Osimertinib (Tagrisso) is an EGFR inhibitor that works against cells with the T790M mutation. Cancer 113(4):847-53 (2008 Aug 15). - Drug Monographs Antiseptic treatment should be continued after systemic therapy has been initiated. Other skin and hair side effects of EGFR inhibitors are mild to moderate alopecia, paronychias, conjunctivitis, hypertrichosis, skin fissures, and generalized pruritus. Trichomegaly may cause visual discomfort, but can be effectively treated by trimming the eye lashes. Burris HA, 3rd, Taylor CW, Jones SF, et al. 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. It can be seen at any time during treatment with EGFR inhibitors. The FDA approved it based on phase II data showing promising response rates; however, in 2005, the labeling was revised as a result of failure of the phase III trial data to show a benefit over placebo.4 Gefitinib is an oral tablet dosed at 250 mg daily and is a small molecule TKI. The characteristic distribution pattern is similar to that of acne vulgaris, but there are no comedones present. Burtness B, Goldwasser MA, Flood W, et al. Epidermal growth factor receptor (EGFR) inhibitors are an increasingly important treatment option for metastasized cancer in patients. Copyright © 2020 Haymarket Media, Inc. All Rights Reserved At the start of your treatment your doctor will ask about your normal As of July 2010, there are two monoclonal antibodies (cetuximab, Erbitux® and panitumumab, Vectibix®) and one receptor tyrosine kinase inhibitor (Gefitinib, Iressa®) that are currently licensed for clinical use in many countries.1 Gefitinib is a historic tyrosine kinase inhibitor that did not show significant survival benefit.4 Lapatinib (Tykerb®/Tyverb®) and canertinib (CI-1033) are currently developed tyrosine kinase inhibitors.4-5 Lapatinib is under investigation for the second-line treatment of metastatic colorectal cancer, whereas canertinib is being studied for progressive, recurrent, locally advanced or metastatic non-small cell lung carcinoma, and metastatic breast cancers.6,7, The safety profile of EGFR-inhibitors is characterized by a class effect comprised of unique skin reactions, including acneiform rash, xerosis, eczema, paronychia, and changes in the hair and nails.8 Hyperpigmentation, trichomegaly, and telangiectasia are less commonly seen. In the majority of randomised clinical studies, in less than 8% of patients toxicity led to the discontinuation of treatment [2, 3, 23]. Paronychia and alterations in hair growth are less common and generally seen after a longer period of treatment. Cetuximab-induced acne. Arora A, Scholar EM. Under current labeling, it is available only to patients who were taking the drug before its use was restricted who have proven continued radiographic response to the drug. - Conference Coverage 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? Your use of this website constitutes acceptance of Haymarket Media’s Privacy Policy and Terms & Conditions. N Engl J Med 351(4):337-45 (2004 Jul 22). Eames T, Kroth J, Flaig MJ, et al. 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. 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. Hautarzt 58(7):615-8 (2007 Jul). CTRL + SPACE for auto-complete. One such mutation is known as T790M. Call your doctor for medical advice about side effects. Br J Dermatol 144(6):1169-76 (2001 Jun). enrolled EGFR mutation-positive NSCLC patients with acquired resistance to EGFR-TKI therapy. Mendelsohn J, Baselga J. J Clin Oncol 23(34):8646-54 (2005 Dec 1). Perifollicular xanthomas associated with epidermal growth factor receptor inhibitor therapy. Write CSS OR LESS and hit save. Klein E, Tietze J, Wollenberg A. Unerwünschte kutane arzneimittelwirkungen von EGF-rezeptor-antagonisten und deren behandlung. Daily online exclusives cover late breaking oncology news, safe handling and administration of chemotherapy drugs, side effect management, and new developments in specific cancers. It tends to be associated with dry skin and at times can be diffuse and very disruptive to activities of daily living. Finally, antisense oligonucleotides specific for the EGFR or EGFR ligand messenger ribonucleic acids (RNAs) may decrease EGFR expression, thus resulting in inhibition of proliferation and induction of apoptosis. J Dermatol Sci 42(2):91-9 (2006 May). Rash is one of the most common toxicities in patients treated with EGFR inhibitors. Sign in Gefitinib (Iressa) was the first EGFR inhibitor to become available in the United States. Ocvirk J, Rebersek M. Managing cutaneous side effects with K1 vitamin creme reduces cutaneous toxicities induced by cetuximab. Modest increases in plasma substance P (SP) occurred at 3 (+27%) and 9 (+25%) weeks. The development of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) has dramatically improved the prognosis of patients with EGFR-mutant non-small-cell lung cancer (NSCLC). Appearance of more severe rash has been correlated with better treatment outcomes. Drug Saf 14(6):375-85 (1996 Jun). 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. You may report side effects to FDA at 1-800-FDA-1088. J Pharmacol Exp Ther 315(3):971-9 (2005 Dec). Erlotinib is orally available, which can aid or cause challenges in adherence. receiving EGFR TKI therapy rarely demonstrate T790M resistance mutations, which is consistent with a pharmacological rather than biological mechanism [44,45]. Table 1 provides information on incidence and severity. A 60-year-old man with an 8-year history of CML was diagno… J Dtsch Dermatol Ges 3(8):599-606 (2005 Aug). Xerosis and fissures are complications appearing in later treatment phases. The sebaceous glands are usually not affected. But eventually these drugs stop working for most people, usually because the cancer cells develop another mutation in the EGFR gene. Plasma magnesium decreased progressively between 3-9 weeks (-9 to -26%). 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. Xerosis may progress to chronic asteatotic eczema and become infected with Staphylococcus aureus or herpes simplex virus. Laura Maximiliane Ehmann, MD, Thomas Ruzicka, MD and Andreas Wollenberg, MD Appropriate judgment regarding switching from one EGFR-TKI to another may improve the performance status and prognosis of patients with EGFR mutation-positive NSCLC. Bierhoff E, Seifert HW, Dirschka T. [Cutaneous lesions due to inhibition of epidermal growth factor receptor]. The development of a papulopustular, follicular exanthema during the first weeks of therapy correlates with therapeutic benefit. Tyrosine kinase inhibitor (TKI) combination is expected to increase in the era of precision medicine. Use favorite eye drops as much as possible. The most common localisation of the skin side ef-fects of the TKI EGFR therapy is the head and trunk area. Patients treated with EGFR inhibitors very likely develop cutaneous side effects. Other less common GI side effects can be nausea and vomiting, anorexia, and stomatitis. This is a common side-effect of TKI medications. GIOTRIF ® (afatinib) has a well-characterised side effects profile 1-5. Download this brochure for patients suffering with EGFRI side effects. Switching EGFR-TKIs because of adverse events provided a clinical benefit for patients with EGFR mutation-positive NSCLC. EGFR inhibitors can often shrink tumors for several months or more. 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). 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. Lane P, Williamson DM. Rationale of a new concept. Hautarzt 57(6):509-13 (2006 Jun). © SkinTherapyLetter. - Full-Length Features Segaert S, Van Cutsem E. 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