Phase I Evaluation of CCNU (Lomustine) in Tumor‐Bearing Cats

Abstract

l‐(2‐Chloroethyl)3‐cyclohexyl‐l‐nitrosourea (CCNU) is an alkylating agent in the nitrosourea subclass. A prospective evaluation of CCNU was done to determine the maximally tolerated dosage of CCNU in tumor‐bearing cats. Response data were obtained when available. Twenty‐five cats were treated with CCNU at a dosage of 50–60 mg/m2 body surface area. Complete hematologic data were available for 13 cats. Neutropenia was the acute dose‐limiting toxicity. The median neutrophil count at the nadir was 1,000 cells/μL (mean, 2,433 cells/μL; range, 0–9,694 cells/μL). The time of neutrophil nadir was variable, occurring 7–28 days after treatment, and counts sometimes did not return to normal for up to 14 days after the nadir. Based on these findings, a 6‐week dosing interval and weekly hematologic monitoring after the 1st treatment with CCNU are recommended. The nadir of the platelet count may occur 14–21 days after treatment. The median platelet count at the nadir was 43,500 cells/μL. No gastrointestinal, renal, or hepatic toxicities were observed after a single CCNU treatment, and additional studies to evaluate the potential for cumulative toxicity should be performed. Five cats with lymphoma and 1 cat with mast cell tumor had measurable responses to CCNU. Phase II studies to evaluate antitumor activity should be completed with a dosing regimen of 50–60 mg/m2 every 6 weeks.