Erlotinib-induced Adverse Skin Reactions

Erlotinib is low molecular-weight quinazolin derivatives which selectively inhibit the epidermal growth factor receptor (EGF-R) tyrosine kinase activity of the intracellular domain, block autophosphorylation and the subsequent signaling cascades. EGF-R is expressed on basal keratinocytes, sebocytes, the outer root sheath of hairs, and endothelial cells in the skin, and plays important roles in the regulation of differentiation, proliferation, apoptosis, attachment and migration of keratinocytes, inflammation, and wound healing. Therefore, inhibition of EGF-R causes a number of cutaneous adverse reactions. Among them, severe skin lesions are very stressful, and impair quality of life of patients. Moreover, they even bring disadvantages such as drug withdrawal or interruption. Several review papers describe representative or common skin lesions which appear either during the first a few weeks or at later phases. Common skin manifestations include papular and pustular follicular eruptions (acneiform eruption), xerosis, paronychia, pruritus, and abnormalities of hairs; however, other than those eruptions, several unusual lesions are also induced. Early intervention of dermatologists and management of skin lesions are quite important, because discontinuance of the drug is unfavorable for patients with clinical benefits for cancers. In this brief review, various cutaneous manifestations seen in Japanese patients treated with erlotinib (Tarceva) are shown, and current management of representative severe conditions is also described.