title: Phase I evaluation of CCNU (lomustine) in tumor-bearing cats.
abstract: 1-(2-Chloroethyl)3-cyclohexyl-1-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/m3 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/microL (mean, 2,433 cells/microL; range, 0-9,694 cells/microL). 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/microL. 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/m3 every 6 weeks.
authors.affiliation: Harrington Oncology Program, Tufts University, School of Veterinary Medicine, North Grafton, MA, USA. kmr32@cornell.edu
authors.forename: K M
authors.initials: KM
authors.lastname: Rassnick
authors.forename: T L
authors.initials: TL
authors.lastname: Gieger
authors.forename: L E
authors.initials: LE
authors.lastname: Williams
authors.forename: D M
authors.initials: DM
authors.lastname: Ruslander
authors.forename: N C
authors.initials: NC
authors.lastname: Northrup
authors.forename: O
authors.initials: O
authors.lastname: Kristal
authors.forename: N C
authors.initials: NC
authors.lastname: Myers
authors.forename: A S
authors.initials: AS
authors.lastname: Moore
mesh_terms: D000284:Administration, Oral; D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage / Q000627:therapeutic use*; D002371:Cat Diseases / Q000188:drug therapy*; D002415:Cats; D005260:Female; D008130:Lomustine / Q000008:administration & dosage / Q000627:therapeutic use*; D008223:Lymphoma / Q000188:drug therapy / Q000662:veterinary*; D008297:Male; D011446:Prospective Studies; D016896:Treatment Outcome
chemical_list: D018906:Antineoplastic Agents, Alkylating; D008130:Lomustine