This trial demonstrated an efficacy benefit with a more amenable side effect profile (AURA; NCT01802632). J Clin Oncol 25(34):5390-6 (2007 Dec 1). - And More, Close more info about Managing EGFR inhibitor side effects in lung cancer patients, Prevention and management of hand-foot syndromes. The characteristic distribution pattern is similar to that of acne vulgaris, but there are no comedones present. Laura Maximiliane Ehmann, MD, Thomas Ruzicka, MD and Andreas Wollenberg, MD In the majority of randomised clinical studies, in less than 8% of patients toxicity led to the discontinuation of treatment [2, 3, 23]. J Am Acad Dermatol 54(2):258-65 (2006 Feb). Cetuximab-induced acne. 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. 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). 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. 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. Write CSS OR LESS and hit save. Erlotinib is a small molecule. 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. 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). Segaert S, Van Cutsem E. Clinical signs, pathophysiology and management of skin toxicity during therapy with epidermal growth factor receptor inhibitors. Lung cancer is the leading cause of cancer deaths in the United States, resulting in more deaths per year than breast, colon, prostate, and pancreatic cancers combined.1 In the past 5 to 10 years, significant advances in treatment have emerged, which have improved overall survival as well as response rates for metastatic non-small cell lung cancer (NSCLC). According to the data from the clinical trials more than 70% of patients treated with the TKI EGFR expe-rience skin side effects [6]. Read full chapter. Allergo J 15:559-65 (2006). This is a common side-effect of TKI medications. Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. Thus, concurrent use of an EGFR TKI with chemotherapy in the first-line setting remains investigational. Lane P, Williamson DM. 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. Grade 3/4 rash occurred in 9% of patients, and grade 3/4 diarrhea developed in 6% of patients.2. 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 . 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. Enjoying our content? Erlotinib is orally available, which can aid or cause challenges in adherence. ILD is an acute inflammation of lung tissue as a reaction to the drug and is a reason for permanent discontinuation of therapy. Understand EGFR TKI Side Effects: To compare Tarceva with chemotherapy for the initial treatment of advanced NSCLC that tests positive for an EGFR mutation, researchers conducted a study among 165 patients with Stage IIIB or Stage IV NSCLC. Rationale of a new concept. Different strategies for EGFR inhibition have been described,3 two of which entered routine clinical use: EGFR-targeting monoclonal antibodies (MoAbs) bind specifically to the extracellular domain of the receptor and competitively inhibit ligand binding,1 and tyrosine kinase inhibitors suppress EGFR signaling at the intracellular domain of the receptor.1 Experimental data exist for EGFR ligand toxin and EGFR immunotoxin conjugates. It is available as an intravenous drug. Drug Saf 14(6):375-85 (1996 Jun). Sapadin AN, Fleischmajer R. Tetracyclines: nonantibiotic properties and their clinical implications. Dermatol Clin 25(2):133-5 (2007 Apr). EGFR inhibitors are associated with a unique group of class- specific cutaneous toxicities, which include acneiform eruptions, paronychia, xerosis, hyperpigmentation, trichomegaly, and telangiectasia. At the start of your treatment your doctor will ask about your normal 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. But eventually these drugs stop working for most people, usually because the cancer cells develop another mutation in the EGFR gene. Infusion reactions have been seen with cetuximab, which is a monoclonal antibody with some murine properties. You’ve viewed {{metering-count}} of {{metering-total}} articles this month. 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. 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). 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. Calculated antibiotic treatment of paronychia is recommended with oral cephalosporines, but oral fluoroquinolones may also be used, especially if Gram-negative infection is suspected. Severe diarrhea occurred in about 3% to 6% of the patients taking erlotinib, cetuximab, or gefitinib in phase III trials. Severe cases of pulpitis sicca (dry skin on the tips of the fingers and toes) with painful rhagades have also been described.4,8, First-line treatment of xerosis is the liberal use of emollients, which should be started within the first days of initiating EGFR inhibitor treatment. J Clin Oncol 26(suppl):abstract 20750 (2008). It tends to be associated with dry skin and at times can be diffuse and very disruptive to activities of daily living. CT of the chest is often diagnostic and shows an inflammatory process within the lungs. Tyrosine kinase inhibitor (TKI) combination is expected to increase in the era of precision medicine. 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. Silver nitrate solution, creams containing urea under plastic occlusion, and topical antibiotics can be used. Many EGFR inhibitors are given orally and present new challenges for oncology nurses, pharmacists, and physicians. The development of a papulopustular, follicular exanthema during the first weeks of therapy correlates with therapeutic benefit. The most common side effect of anti-EGFR therapy is skin toxicity, which is generally mild to moderate, but may be severe in up to 18% of patients. Patients treated with EGFR inhibitors very likely develop cutaneous side effects. enrolled EGFR mutation-positive NSCLC patients with acquired resistance to EGFR-TKI therapy. Xerosis (dryness of the skin) is a common side effect caused by EGFRI therapy, occurring in up to 35% of individuals . Cancer 113(4):847-53 (2008 Aug 15). anti-EGFR, epidermal growth factor receptor inhibitors, cutaneous side-effects, acneiform eruption, paronychia, xerosis, management, The epidermal growth factor receptor (EGFR), a 170-kd transmembrane glycoprotein, is a member of the type 1 receptor tyrosine kinase (TK) family. Evidence-based practice for the unique side effects associated with EGFR inhibitors is still evolving. Katzer K, Tietze J, Klein E, et al. Eur J Dermatol 20(1):82-4 (2010 Jan-Feb). EGFR inhibitors very likely develop cutaneous side effects. Use favorite eye drops as much as possible. [Therapy of severe cetuximab-induced acneiform eruptions with oral retinoid, topical antibiotic and topical corticosteroid]. Clinical studies have shown that metformin and EGFR-TKI have synergistic effects in … 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. The most common localisation of the skin side ef-fects of the TKI EGFR therapy is the head and trunk area. 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 … Some patients may also experience dryness of vaginal and perineal regions. 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