Low apparent risk of CCNU (lomustine)-associated clinical hepatotoxicity in cats

Abstract

The purpose of this study was to evaluate the prevalence of serum alanine transaminase (ALT) increases in cats treated with 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU, lomustine). The medical records of 95 cats treated with CCNU were reviewed, 29 of which met study criteria (at least one treatment with CCNU as a single agent, and at least one pretreatment and one post-treatment complete biochemical profile). Cats that received concurrent prednisone or dexamethasone were included, but those that received concurrent hepatoprotective or hepatotoxic medications were excluded. Cats included in the study were diagnosed with hepatic carcinoma, mammary carcinoma, lymphoma, mast cell tumor, plasma cell tumor and gastrointestinal leiomyoma. CCNU was given as a single agent at 31-60 mg/m(2), once every 4-8 weeks. Serum alanine transaminase (ALT) activity was measured after at least one dose of CCNU. Four cats (13.7%) had increased ALT activity above the reference interval before starting treatment. Two additional cats (6.8%) developed increased ALT activity above the reference interval 1 month after treatment with CCNU. One cat developed clinical signs potentially associated with hepatotoxicity, without a concurrent increase in ALT, 3 weeks following the final dose of CCNU. No association between dosing frequency, cumulative dose, initial starting dose or concurrent medications, and increases in ALT were found. Clinically significant hepatic injury is seemingly uncommon in cats treated with CCNU.