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Hepatotoxicity associated with CCNU (lomustine) chemotherapy in dogs
Orna Kristal1, Kenneth M Rassnick, John M Gliatto
1Harrington Oncology Program, Tufts University School of Veterinary Medicine, North Grafton, MA, USA.
Journal of Veterinary Internal Medicine
|February 10, 2004
Summary
The chemotherapy drug lomustine (CCNU) can cause delayed, cumulative liver damage in dogs. This hepatotoxicity is often irreversible, dose-related, and can be fatal, requiring careful monitoring during treatment.
Area of Science:
- Veterinary Medicine
- Oncology
- Toxicology
Background:
- 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) is a chemotherapy agent used in veterinary oncology.
- Hepatic toxicity is a potential side effect of chemotherapy, but its specific characteristics with CCNU in dogs require further elucidation.
Purpose of the Study:
- To investigate the incidence, characteristics, and outcomes of CCNU-induced hepatic toxicity in tumor-bearing dogs.
Main Methods:
- Retrospective analysis of 179 tumor-bearing dogs treated with CCNU (50-110 mg/m2 PO) between 1995 and 2001.
- Monitoring for hepatic toxicity, including biochemical assays, diagnostic imaging, liver biopsies, and survival analysis.
Main Results:
- 11 dogs (6.1%) developed hepatic toxicity, with higher median CCNU doses and treatment frequency in affected dogs.
- Toxicity onset was delayed (median 11 weeks), characterized by elevated liver enzymes, hypoalbuminemia, ascites, and pleural effusion.
- Liver biopsies showed nonspecific chronic changes; 7 dogs died from liver failure, with persistent biochemical and histopathologic abnormalities in survivors.
Conclusions:
- CCNU can induce delayed, cumulative, dose-related, and potentially fatal chronic hepatotoxicity in dogs.
- The observed liver damage may be irreversible, highlighting the need for vigilant monitoring and potential dose adjustments during CCNU therapy.