Abstract
Recent developments and therapeutic use of selective BRAF inhibitors (e.g. dabrafenib and vemurafenib) have significantly improved overall survival and disease-free survival of patients with BRAF V600 mutation-positive metastatic melanoma. Despite their survival benefits, small-molecule inhibitors of BRAF are associated with significant and sometimes severe treatment-related dermatological toxicity. The most common adverse skin reactions include photosensitivity, induced malignant lesions of the skin such as keratoacanthomas, squamous cell carcinoma and new primary melanomas, as well as keratinocyte proliferation and differentiation dysfunctions that can manifest as skin papillomas, hand-foot skin reaction, keratosis pilaris-like rash, acantholytic dyskeratosis and cysts of the milia type. In this article, we describe the clinical and histological features of the cutaneous manifestations induced by vemurafenib and dabrafenib on the basis of our clinical experience and a literature review. The crucial role of dermatologists in patient management is also highlighted.
Keywords:
BRAF; Dabrafenib; Dermatologic adverse events; Effets indésirables cutanés; Malignant melanoma; Mélanome; Vemurafenib.
Copyright © 2013 Elsevier Masson SAS. All rights reserved.
MeSH terms
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Acantholysis / chemically induced
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Alopecia / chemically induced
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Antineoplastic Agents / adverse effects*
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Antineoplastic Agents / therapeutic use
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Carcinoma, Squamous Cell / chemically induced
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Codon / genetics
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Drug Eruptions / etiology*
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Hand-Foot Syndrome / etiology
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Humans
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Imidazoles / adverse effects*
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Imidazoles / therapeutic use
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Indoles / adverse effects*
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Indoles / therapeutic use
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Keratoacanthoma / chemically induced
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Keratosis / chemically induced
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Melanoma / chemically induced
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Melanoma / drug therapy
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Neoplasm Proteins / antagonists & inhibitors*
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Neoplasm Proteins / genetics
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Neoplasms, Second Primary / chemically induced
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Nevus / chemically induced
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Oximes / adverse effects*
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Oximes / therapeutic use
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Panniculitis / chemically induced
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Photosensitivity Disorders / chemically induced
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Protein Kinase Inhibitors / adverse effects*
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Protein Kinase Inhibitors / therapeutic use
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Proto-Oncogene Proteins B-raf / antagonists & inhibitors*
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Proto-Oncogene Proteins B-raf / genetics
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Radiodermatitis / chemically induced
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Skin Neoplasms / chemically induced
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Skin Neoplasms / drug therapy
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Sulfonamides / adverse effects*
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Sulfonamides / therapeutic use
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Vemurafenib
Substances
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Antineoplastic Agents
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Codon
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Imidazoles
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Indoles
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Neoplasm Proteins
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Oximes
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Protein Kinase Inhibitors
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Sulfonamides
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Vemurafenib
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BRAF protein, human
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Proto-Oncogene Proteins B-raf
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dabrafenib