title: Prospective randomized clinical trial assessing the efficacy of Denamarin for prevention of CCNU-induced hepatopathy in tumor-bearing dogs.
abstract: BACKGROUND
  Increases in liver enzymes occur in up to 86% of dogs receiving CCNU and can result in treatment delay or early discontinuation of treatment. Denamarin contains S-adenosylmethionine and silybin, both of which have been investigated as treatments for various liver diseases.
  
  
  OBJECTIVE
  Dogs on CCNU receiving Denamarin have lower alanine aminotransferase (ALT) activity than dogs not receiving Denamarin. Dogs on Denamarin are less likely to require treatment delay because of hepatopathy and are more likely to complete their prescribed course of CCNU.
  
  
  METHODS
  Dogs with lymphoma, mast cell tumor, or histiocytic sarcoma that were prescribed CCNU with or without corticosteroids and with normal ALT activity were eligible for enrollment.
  
  
  METHODS
  Dogs were prospectively randomized to receive either concurrent Denamarin during CCNU chemotherapy or to receive CCNU alone. Liver-specific laboratory tests were run before each dose of CCNU.
  
  
  RESULTS
  Increased liver enzyme activity occurred in 84% of dogs receiving CCNU alone and in 68% of dogs on concurrent Denamarin. Dogs receiving CCNU alone had significantly greater increases in ALT, aspartate aminotransferase, alkaline phosphatase, and bilirubin and a significantly greater decrease in serum cholesterol concentrations than dogs receiving concurrent Denamarin. Dogs receiving CCNU alone were significantly more likely to have treatment delayed or discontinued because of increased ALT activity.
  
  
  CONCLUSIONS
  Increased liver enzyme activity occurs commonly in dogs receiving CCNU chemotherapy. These results support the use of concurrent Denamarin to minimize increased liver enzyme activity in dogs receiving CCNU chemotherapy. Denamarin treatment also increases the likelihood of dogs completing a prescribed CCNU course.
authors.affiliation: Department of Surgical and Radiological Sciences, University of California, Davis, Davis, CA 95616, USA. kskorups@ucdavis.edu
authors.forename: K A
authors.initials: KA
authors.lastname: Skorupski
authors.forename: G M
authors.initials: GM
authors.lastname: Hammond
authors.forename: A M
authors.initials: AM
authors.lastname: Irish
authors.forename: M S
authors.initials: MS
authors.lastname: Kent
authors.forename: T A
authors.initials: TA
authors.lastname: Guerrero
authors.forename: C O
authors.initials: CO
authors.lastname: Rodriguez
authors.forename: D W
authors.initials: DW
authors.lastname: Griffin
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001663:Bilirubin / Q000097:blood; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood / Q000473:pathology / Q000517:prevention & control / Q000662:veterinary*; D002784:Cholesterol / Q000097:blood; D004283:Dog Diseases / Q000097:blood / Q000139:chemically induced* / Q000517:prevention & control*; D004285:Dogs; D005260:Female; D008130:Lomustine / Q000009:adverse effects* / Q000627:therapeutic use; D008297:Male; D009369:Neoplasms / Q000097:blood / Q000188:drug therapy / Q000662:veterinary; D011446:Prospective Studies; D012436:S-Adenosylmethionine / Q000008:administration & dosage*; D000077385:Silybin; D012838:Silymarin / Q000008:administration & dosage*; D018709:Statistics, Nonparametric
chemical_list: D012838:Silymarin; D000077385:Silybin; D008130:Lomustine; D012436:S-Adenosylmethionine; D002784:Cholesterol; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000469:Alkaline Phosphatase; D001663:Bilirubin