Cutaneous Side-effects of EGFR Inhibitors and Their Management

Laura Maximiliane Ehmann, MD; Thomas Ruzicka, MD; Andreas Wollenberg, MD

Disclosures

Skin Therapy Letter. 2011;16(1):1-3. 

In This Article

Abstract and Introduction

Abstract

Epidermal growth factor receptor (EGFR) inhibitors are an increasingly important treatment option for metastasized cancer in patients. 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. As a consequence, cutaneous side-effects are frequently observed during cancer therapy with EGFR inhibitors. During the first few weeks of treatment, acneiform eruptions are the earliest common side-effect. Xerosis and fissures are complications appearing in later treatment phases. Paronychia and alterations in hair growth are less common and generally seen after a longer period of treatment. We present an overview of the various cutaneous side-effects associated with EGFR inhibition and discuss their respective therapeutic options.

Introduction

The epidermal growth factor receptor (EGFR), a 170-kd transmembrane glycoprotein, is a member of the type 1 receptor tyrosine kinase (TK) family. The EGFR is physiologically expressed in epithelial tissues and hair follicles, where it contributes to epidermal proliferation, differentiation, and hair growth. 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]

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. These novel drugs are composed of an EGFR ligand or EGFR-binding antibody and a cytotoxic agent. 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.

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. 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]

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