Cutaneous Side Effects of Multikinase Inhibitors Used in Renal Cell Cancer

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Abstract

Paralleling the increasing use of multikinase inhibitors in the field of cancer therapy, patients and clinicians are confronted with frequently occurring cutaneous side effects associated with the use of these new drugs. Two such targeted agents, sunitinib (Sutent) and sorafenib (Nexavar), were recently approved by the US Food and Drug Administration to treat patients with metastatic renal cell cancer (RCC). Cutaneous adverse effects associated with these drugs are sometimes distressing, partly because of their chronicity given the long-term duration of treatments, and can result in treatment interruption. Active collaboration between dermatologists and medical oncologists or urologists is urgently needed to characterize and treat these dermatologic side effects.

Introduction

Sorafenib blocks Raf gene products (serine-threonine kinases), including mutated B-Raf, as well as platelet-derived growth factor-beta (PDGFR-β), FLT₃, and vascular endothelial growth factor receptor-2 and -3 (VEGFR-2 and -3). Sunitinib blocks VEGFR-1, -2, and -3, PDGFR-α and -β, Ret, Kit, and FLT₃. Both drugs were recently approved by the US Food and Drug Administration (FDA) to treat patients with metastatic RCC,^1,2 and sunitinib has also been approved for patients with imatinib (Gleevec)-resistant gastrointestinal stromal tumors.³ Furthermore, both drugs are currently being tested in various tumors (such as sorafenib for hepatocarcinoma) as single agents and in combination with chemotherapy, with promising preliminary results in several tumors. Numerous cutaneous side effects have been observed with these two molecules.⁴ Some side effects are common to the two drugs, such as hand-foot skin reaction (HFSR), xerosis, and subungual splinter hemorrhages (SSH), whereas others, like hair modifications, keratotic papules, and facial erythema, seem to be associated with the use of one or another of these targeted agents. Table 1 shows the association between the targeted receptors and the skin symptoms observed.

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