1. Skin inflammatory response and efficacy of anti-epidermal growth factor receptor therapy in metastatic colorectal cancer (CUTACETUX)
- Author
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David Tougeron, Sheik Emambux, Laure Favot, Thierry Lecomte, Ewa Wierzbicka-Hainaut, Mahtab Samimi, Eric Frouin, Nicolas Azzopardi, Jocelyn Chevrier, Laura Serres, Julie Godet, Pierre Levillain, Gilles Paintaud, Aurélie Ferru, Laetitia Rouleau, Adriana Delwail, Christine Silvain, Jean-Pierre Tasu, Franck Morel, Stéphanie Ragot, Jean-Claude Lecron, Service de Gastroentérologie, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Laboratoire Inflammation, Tissus épithéliaux et Cytokines (LITEC), Université de Poitiers, Service d'Oncologie Médicale, Service de Gastroentérologie [CHRU Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), GICC EA 7501, PATCH (Pharmacologie des anticorps thérapeutiques chez l'Homme) (PATCH), Groupe innovation et ciblage cellulaire (GICC), EA 7501 [2018-...] (GICC EA 7501), Université de Tours (UT)-Université de Tours (UT), Département de Dermatologie [CHU Poitiers], Service de dermatologie (CHRU de Tours), Infectiologie et Santé Publique (UMR ISP), Université de Tours (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Service de Pathologie [CHU Poitiers], Service de pharmacologie, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, ImageUP (Plateforme d'Imagerie de l'Université de Poitiers), Signalisation et Transports Ioniques Membranaires (STIM), Université de Poitiers-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), Service de Radiologie (POITIERS - Radio), Laboratoire de Traitement de l'Information Medicale (LaTIM), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), CIC - Poitiers, Université de Poitiers-Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service Immunologie/Inflammation [CHU Poitiers], Ligue contre le Cancer (départements de la Vienne, des Deux-Sèvres, de la Charente et de la Charente-Maritime), fondation 'Sport et Collection', Institut de Recherche des Maladies de l'Appareil Digestif (IRMAD) grant from Societe Nationale Francaise de Gastro-Enterologie (SNFGE) and Merck Sante SAS (Lyon, France)., Chanteloup, Nathalie Katy, Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest)-IMT Atlantique (IMT Atlantique), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Université de Tours-Université de Tours, Université de Tours-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université de Poitiers-Université de Tours-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), and Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest)-Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM)
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[SDV]Life Sciences [q-bio] ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Antibodies, Monoclonal ,Antineoplastic Agents ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,Skin toxicity ,RC581-607 ,cytokines ,[SDV] Life Sciences [q-bio] ,ErbB Receptors ,inflammatory factors ,[SDV.CAN] Life Sciences [q-bio]/Cancer ,cetuximab ,Humans ,Prospective Studies ,monoclonal antibodies ,Immunologic diseases. Allergy ,Colorectal Neoplasms ,RC254-282 ,Research Article ,Original Research - Abstract
International audience; Anti-epidermal growth factor receptor (EGFR) monoclonal antibody is a standard treatment of metastatic colorectal cancer (mCRC) and its most common adverse effect is a papulopustular acneiform rash. The aim of the CUTACETUX study was to characterize the skin inflammatory response associated with this rash and its relation to treatment efficacy.This prospective study included patients with mCRC treated with first-line chemotherapy plus cetuximab. Patients underwent skin biopsies before the initiation of cetuximab (D0) and before the third infusion (D28), one in a rash zone and one in an unaffected zone. Expression of Th17-related cytokines (IL-17A, IL-21, IL-22), antimicrobial peptides (S100A7 and BD-2), innate response-related cytokines (IL-1 beta, IL-6, TNF-alpha and OSM), T-reg-related cytokines (IL-10 and TGF-beta), Th1-related cytokine (IFN-gamma), Th2-related cytokine (IL-4), Thymic stromal lymphopoietin and keratinocyte-derived cytokines (IL-8, IL-23 and CCL20) were determined by RT-PCR.Twenty-seven patients were included. Levels of most of the cytokines increased at D28 in the rash zone compared to D0. No significant association was observed between variations of cytokines levels and treatment response in the rash zone and only the increase of IL-4 (p = .04) and IL-23 (p = .02) levels between D0 and D28 in the unaffected zone was significantly associated with treatment response. Increased levels of IL-8 (p = .02), BD-2 (p = .02), IL-1 beta (p = .004) and OSM (p = .02) in the rash zone were associated with longer progression-free survival.Expression of Th2-related and keratinocyte-derived cytokines in the skin was associated with anti-EGFR efficacy. If this inflammatory signature can explain the rash, the exact mechanism by which these cytokines are involved in anti-EGFR tumor response remains to be studied.
- Published
- 2020