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.
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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 NSCLCpatients 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.
Authors: Anna E Kersh; Spencer Ng; Yun Min Chang; Maiko Sasaki; Susan N Thomas; Haydn T Kissick; Gregory B Lesinski; Ragini R Kudchadkar; Edmund K Waller; Brian P Pollack Journal: J Clin Pharmacol Date: 2017-11-14 Impact factor: 3.126
Authors: Ronald A Lubet; Eva Szabo; Kenneth K Iwata; Stanley C Gill; Chris Tucker; Ann Bode; Vernon E Steele; M Margaret Juliana; Holly L Nicastro; Clinton J Grubbs Journal: Cancer Prev Res (Phila) Date: 2013-03-26