Cutaneous Lesions in Rats Following Administration of an Irreversible Inhibitor of ErbB Receptors, Including the Epidermal Growth Factor Receptor

The study examined the chronic toxicity of CI-1033, an irreversible inhibitor of erbB receptors, in Wistar rats, focusing on cutaneous lesions as the primary toxicity. Conducted over 27 weeks with 15 male and 15 female rats per group, doses of 2.5, 5, or 10 mg/kg were administered. The study found dose-dependent skin changes, including papules, crusts, scales, and alopecia, particularly severe in females. Microscopic skin changes such as epidermal hyperplasia and folliculitis were observed, correlating with alopecia. Additional effects included hepatic cholestasis and epithelial atrophy in the gastrointestinal tract and vagina. The findings were consistent with known side effects of EGF receptor inhibitors in humans, supporting the use of rats as a model for studying these toxicities. Despite some antitumor effects, the development of CI-1033 was halted due to insufficient efficacy.