Case series of dermatologic events associated with the insulin-like growth factor receptor 1 inhibitor cixutumumab.

The insulin-like growth factor-1 receptor (IGFR1) is frequently overexpressed in a broad range of tumors. Its signaling has been shown to be involved in tumorigenesis and metastatic potential of multiple cancers.1 Drugs targeting this pathway began to be developed in the late 1990s, including monoclonal antibodies to IGFR1.2 Cixutumumab (IMC-A12; ImClone Systems, Bridgewater, NJ), a fully humanized monoclonal IgG1 antibody, binds to IGFR1 with high affinity, inhibiting its activation.3 Because IGFR1-targeted therapy is relatively new, the potential toxicities are not fully understood. IGF-1 has many physiologic roles that could potentially be compromised by the inhibition of its receptor. One of these roles is to enhance epidermal proliferative potential as well as keratinocyte cell migration.4 Therefore, potential dermatologic adverse effects can be anticipated when IGFR1 function is inhibited. An in-depth review of the literature did not reveal any previous reports that have addressed this issue. In this article, we describe four patients who were enrolled onto clinical trials using cixutumumab and subsequently developed skin and nail abnormalities.