Phase I evaluation of CCNU (Lomustine) in tumor-bearing cats

1-(2-Chloroethyl)3-cyclohexyl-1-nitrosourea (CCNU) is an alkylating agent i n the nitrosourea subclass. A prospective evaluation of CCNU was done to de termine the maximally tolerated dosage of CCNU in tumor-bearing cats. Respo nse data were obtained when available. Twenty-live cats were treated with C CNU at a dosage of 50-60 mg/m(2) body surface area. Complete hematologic da ta were available for 13 cats. Neutropenia was the acute dose-limiting toxi city. The median neutrophil count at the nadir was 1,000 cells/muL (mean. 2 .433 cells/muL: range. 0-9.693 cells/muL). The time of neutrophil nadir was variable, occurring 7-28 days after treatment, and counts sometimes did nu t return to normal for up to 14 days alter the nadir Based on these finding s, a 6-week dosing interval and weekly hematologic monitoring after the ist treatment with CCNU are recommended. The nadir of the platelet count may o ccur 14-21 days after treatment. The median platelet count at the nadir was 43.500 cells/muL. No gastrointestinal, renal, or hepatic toxicities were o bserved after a single CCNU treatment, and additional studies to evaluate t hr potential for cumulative toxicity should he performed. Five cats with ly mphoma and 1 cat with mast cell tumor had measurable responses to CCNU, Pha se II studies to evaluate antitumor activity should be completed with a dos ing regimen of 50-60 mg/m(2) every 6 weeks.