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Eur J Cancer. 2010 Jul;46(11):2010-9. doi: 10.1016/j.ejca.2010.04.028. Epub 2010 Jun 2.

Characterisation of the cutaneous pathology in non-small cell lung cancer (NSCLC) patients treated with the EGFR tyrosine kinase inhibitor erlotinib.

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  • 1The Laboratory for Investigative Dermatology, The Rockefeller University, NY 10065, USA.

Abstract

INTRODUCTION:

EGFR inhibitors (EGFRIs) have been shown to be clinically effective in various cancers. Unique skin toxicity is commonly observed with EGFRIs and a correlation between the clinical benefit of EGFRIs and this characteristic rash has been reported. Erlotinib is a potent EGFRI approved for treatment of non-small cell lung cancer (NSCLC) and pancreatic cancer.

METHODS:

This is the first time in which patients were given increasing doses of an EGFRI to induce a mechanistic rash and study its associated pathology in skin. Biopsies were collected during treatment from both rash-affected and unaffected skin of 23 NSCLC patients and compared with pre-treatment biopsies.

RESULTS:

Altered differentiation of appendegeal epithelium (hair follicles and sebaceous glands) was remarkable in both affected and unaffected skin, although epidermal growth was not significantly reduced. A predominantly mononuclear leucocyte infiltrate was detected in the interfollicular dermis or around skin appendages. This infiltrate included TRAIL-positive cells with a dendritic cell (DC) morphology, although T-cells, antigen-presenting DCs and macrophages were also evident. This is the first report showing the involvement of a dendritic cell subtype with EGFRI skin toxicity.

CONCLUSIONS:

Altered differentiation of pilosebaceous epithelium is evident in both rash-affected and unaffected skin and constitutes the primary process of EGFRI in human skin. We propose that this eventually triggers inflammation and the EGFRI rash. TRAIL-positive inflammatory cells could link rash development and immune-triggered apoptosis of epithelial cells, including those of underlying carcinomas.

Copyright 2010 Elsevier Ltd. All rights reserved.

[PubMed - indexed for MEDLINE]
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