Prospective randomized clinical trial assessing the efficacy of Denamarin for prevention of CCNU-induced hepatopathy in tumor-bearing dogs

J Vet Intern Med. 2011 Jul-Aug;25(4):838-45. doi: 10.1111/j.1939-1676.2011.0743.x. Epub 2011 Jun 20.


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.

Hypothesis: 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.

Animals: 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.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alanine Transaminase / blood
  • Alkaline Phosphatase / blood
  • Animals
  • Aspartate Aminotransferases / blood
  • Bilirubin / blood
  • Chemical and Drug Induced Liver Injury / blood
  • Chemical and Drug Induced Liver Injury / pathology
  • Chemical and Drug Induced Liver Injury / prevention & control
  • Chemical and Drug Induced Liver Injury / veterinary*
  • Cholesterol / blood
  • Dog Diseases / blood
  • Dog Diseases / chemically induced*
  • Dog Diseases / prevention & control*
  • Dogs
  • Female
  • Lomustine / adverse effects*
  • Lomustine / therapeutic use
  • Male
  • Neoplasms / blood
  • Neoplasms / drug therapy
  • Neoplasms / veterinary
  • Prospective Studies
  • S-Adenosylmethionine / administration & dosage*
  • Silybin
  • Silymarin / administration & dosage*
  • Statistics, Nonparametric


  • Silymarin
  • Silybin
  • Lomustine
  • S-Adenosylmethionine
  • Cholesterol
  • Aspartate Aminotransferases
  • Alanine Transaminase
  • Alkaline Phosphatase
  • Bilirubin