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ABSTRACT
Targeted therapies are gaining field in oncology practice. Some of them are already well established, others are upcoming. They target cancer cells more selectively, therefore causing less collateral damage. Dermatologic side effects are common and sometimes class specific. The skin toxicity profile of EGFR inhibitors, MEK en Raf inhibitors, mTOR inhibitors, VEGF targeting molecules, multikinase inhibitors, the HER2 monoclonal antibody trastuzumab and the CTLA-4 monoclonal antibodies are discussed. When possible, a pathogenic mechanism and treatment options are described.
Key words: Skin toxicity, targeted therapy, oncology
INTRODUCTION
In recent years multiple targeted therapies have emerged in the fi eld of oncology. In contrast to conventional chemotherapy they are believed to target cancer cells in a more specifi c way, thereby reducing collateral damage. Along with these new families of drugs new side eff ects arose, especially in the fi eld of dermatology. The aim of this paper is to describe the cutaneous side eff ects of the most frequently used targeted therapies (table 1) and to clarify a pathogenic mechanism where possible. Symptomatic treatment strategies are suggested. In case of high grade toxicity, dose reduction or discontinuation of the drug has to be considered.
SKIN TOXICITY OF EGFR INHIBITORS
The Epidermal Growth Factor Receptor in the skin is primarily expressed in undiff erentiated, proliferating keratinocytes which are mainly present in the basal layer of the epidermis and the outer root sheath of hair follicles. EGFR activation in skin is important for normal keratinocyte proliferation, migration, diff erentiation and survival (1). Disruption of this normal signalling leads to acute keratinocyte stress, cytokine release and infl ammation (2).
Dermatological side eff ects of EGFR inhibitors are a papulopustular rash, xerosis, pruritus, nail and hair abnormalities (3). There are currently no randomized controlled trials defi ning the best treatment options for these side eff ects. Current management guidelines are based on empirical data and are further substantiated by increasing insights in the pathogenic mechanisms.
Papulopustular eruption
A papulopustular eruption is observed within 5 to 14 days after start of therapy in 53 to 100% of the patients (4). Maximum severity is reached in the second week and a partial or complete resolution without scarring is possible despite continuation of the therapy (5). The eruption is dose-dependent...