Hepatotoxicity Associated with CCNU (Lomustine) Chemotherapy in Dogs

Journal of Veterinary Internal Medicine

Volumn 18, Issue 1, 2004, Pages 75-80

  Kristal, Orna ^a,b   Rassnick, Kenneth M ^a,c   Gliatto, John M ^a,d   Northrup, Nicole C ^a,e   Chretin, John D ^a   Morrison Collister, Kirsten ^a   Cotter, Susan M ^a   Moore, Antony S ^a  

^a TUFTS UNIVERSITY   (United States)

^b Veterinary Oncology Services   (United States)

^c Department of Obstetrics Gynecology   (United States)

^d ANTECH DIAGNOSTICS   (United States)

^e UNIVERSITY OF GEORGIA   (United States)

Author keywords

Alkylating agent; Cancer; Canine; Liver; Neoplasia; Nitrosourea; Toxicity

Indexed keywords

ANTINEOPLASTIC AGENT; BILE ACID; LIVER ENZYME; LOMUSTINE;

ANIMAL TISSUE; ARTICLE; ASCITES; BILE ACID BLOOD LEVEL; CANCER CHEMOTHERAPY; CANCER SURVIVAL; CAUSE OF DEATH; CHRONIC TOXICITY; CLINICAL FEATURE; CONTROLLED STUDY; DOG DISEASE; DOSE RESPONSE; DRUG RESPONSE; ECHOGRAPHY; ENZYME ACTIVITY; ENZYME BLOOD LEVEL; HISTOPATHOLOGY; HYPOALBUMINEMIA; LIVER BIOPSY; LIVER FAILURE; LIVER TOXICITY; NONHUMAN; PLEURA EFFUSION; TUMOR;

ADMINISTRATION, ORAL; ANIMALS; ANTINEOPLASTIC AGENTS, ALKYLATING; DOG DISEASES; DOGS; FEMALE; HEPATITIS, TOXIC; LOMUSTINE; MALE; MASSACHUSETTS; RECORDS; RETROSPECTIVE STUDIES; RISK FACTORS;

ANIMALIA; CANIS FAMILIARIS;

EID: 0842330494     PISSN: 08916640     EISSN: None     Source Type: Journal    
DOI: 10.1892/0891-6640(2004)18<75:HAWCLC>2.0.CO;2     Document Type: Article

References (36)

1. Tew KD, Colvin M, Chabner BA. Alkylating agents. In: Chabner BA, Longo DL, eds. Cancer Chemotherapy and Biotherapy, 2nd ed. Philadelphia, PA: Lippincott-Raven; 1996:297-332.
2. Oliverio VT, Wesley M, Vietzke MK, et al. The absorption, distribution, excretion, and biotransformation of the carcinostatic 1-(2-chloroethyl)-3- cyclohexyl-1-nitrosourea in animals. Cancer Res 1970; 30:1330-1337.
3. Hill DL, Kirk MC, Struck RF. Microsomal metabolism of nitrosoureas. Cancer Res 1975;35:296-301.
4. Lee FYF, Workman P, Roberts JT, Bleehen NM. Clinical pharmacokinetics of oral CCNU (Lomustine). Cancer Chemother Pharmacol 1985;14:125-131.
5. Weiss RB, Issell B. The nitrosoureas: Carmustine (BCNU) and lomustine (CCNU). Cancer Treat Rev 1982;9:313-330.
6. Hoogstraten B, Gottlieb JA, Caoili E, et al. CCNU (1-[2-chloroethyl]-3- cyclohexyl-1-nitrosourea, NSC-79037) in the treatment of cancer. Phase II study. Cancer 1973;32:38-43.
7. Hoogstraten B, Haas CD, Haut A, et al. CCNU and bleomycin in the treatment of cancer: A southwest oncology group study. Med Pediatr Oncol 1975;1:95-106.
8. Moertel CG, Schutt AJ, Reitemeier RJ, Hahn RG. A phase II study of 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (NSC-9037) in the palliative management of advanced gastrointestinal cancer. Cancer Res 1972;32:1278-1279.
9. Wilson CB, Gutin P, Boldrey EB, et al. Single-agent chemotherapy of brain tumors. Arch Neurol 1976;33:739-744.
10. Fulton LM, Steinberg HS. Preliminary study of lomustine in the treatment of intracranial masses in dogs following localization by imaging techniques. Semin Vet Med Surg (Small Anim) 1990;5:241-245.
11. Rassnick KM, Moore AS, Williams LE, et al. Treatment of canine mast cell tumors with CCNU (Lomustine). J Vet Intern Med 1999; 13:601-605.
12. Moore AS, London CA, Wood CA, et al. Lomustine (CCNU) for the treatment of resistant lymphoma in dogs. J Vet Intern Med 1999;13:395-398.
13. Ellis ME, Weiss RB, Kupermine M. Nephrotoxicity of lomustine. Cancer Chemother Pharmacol 1985;15:174-175.
14. Carter SK, Newman JW. Nitrosoureas: 1,3-bis (2-chloroethyl) -1-nitrosourea (NSC-409962; BCNU) and 1-(2-chloroethyl)-3-cyclohexyl-1- nitrosourea (NSC-79037; CCNU) - Clinical brochure. Cancer Chemother Rep 1968;1(Part 3):115-151.
15. Schaeppi U, Fleischman RW, Phelan RS, et al. CCNU (NSC-79037): Preclinical toxicologic evaluation of a single intravenous infusion in dogs and monkeys. Cancer Chemother Rep 1974;5(Part 3): 53-64.
16. Abb J, Netzel B, Rodt HV, Thierfelder S. Autologous bone marrow grafts in dogs treated with lethal doses of 1-(2-chloroethyl)-3-cyclohexyl-1- nitrosourea. Cancer Res 1978;38:2157-2159.
17. Henry MC, Marlow M. Serum enzymes in hepatotoxicity induced by chloroethylcyclohexyl nitrosourea and arabinofuranosyl-6-mercaptopurine. Toxicol Appl Pharmacol 1973;24:250-255.
18. Henry MC, Schein PS. Hepatotoxicity of 1-(2-chloroethyl)-3-cyclohexyl-1- nitrosourea (CCNU) in dogs: The use of serial percutaneous liver biopsies. Toxicol Appl Pharmacol 1973;25:410-417.
19. Dawson B, Trapp RG. Basic and Clinical Biostatistics, 3rd ed. New York: Lange Medical Books/McGraw-Hill; 2001.
20. Ahmed AE, Grissom M, el-Azhary R, et al. Studies on the mechanism of 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU)-induced hepatotoxicity. II. Biochemical and morphological characterization of the injury and its prevention by phenobarbital. Cancer Chemother Pharmacol 1987;19:103-108.
21. Kretschmer NW, Boor PJ, el-Azhary RA, et al. Studies on the mechanism of 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU)-induced hepatotoxicity. III. Ultrastructural characterization of bile duct injury. Cancer Chemother Pharmacol 1987;19:109-117.
22. Ducastelle T, Raguenez-Viotte G, Fouin-Fortunet H, et al. The hepatotoxicity of 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) in rats. Ultrastructural evidence of a delayed microtubular toxicity. Cancer Chemother Pharmacol 1988;22:153-162.
23. Tiwari BP, Ramanathan P, Patel RB, et al. Animal model for liver dysfunction using lomustine in Wistar rats. Indian J Gastroenterol 2000;19:9-11.
24. Laquerriere A, Raguenez-Viotte G, Paraire M, et al. Nitrosoureas lomustine, carmustine and fotemustine induced hepatotoxic perturbations in rats: Biochemical, morphological and flow cytometry studies. Eur J Cancer 1991;27:630-638.
25. Bono VH. Review of the mechanism of action studies of the nitrosoureas. Cancer Treat Rep 1976;60:699-702.
26. Kahn S, Ramwani JJ, O'Brien PJ. Hepatocyte toxicity of mechlorethamine and other alkylating anticancer drugs. Biochem Pharmacol 1992;43:1963-1967.
27. Center SA. Diagnostic procedures for evaluation of hepatic disease. In: Guilford WG, Center SA, Strombeck DR, et al, eds. Strombeck's Small Animal Gastroenterology, 3rd ed. Philadelphia, PA: WB Saunders; 1996:130-188.
28. Center SA. Pathophysiology of liver disease: Normal and abnormal function. In: Guilford WG, Center SA, Strombeck DR, et al, eds. Strombeck's Small Animal Gastroenterology, 3rd ed. Philadelphia, PA: WB Saunders; 1996:553-632.
29. Steyn PF, Wittum TE. Radiographic, epidemiologic, and clinical aspects of simultaneous pleural and peritoneal effusions in dogs and cats: 48 cases (1982-1991). J Am Vet Med Assoc 1993;202:307-312.
30. Lazaridis KN, Frank JW, Krowka MJ, Kamath PS. Hepatic hydrothorax: Pathogenesis, diagnosis, and management. Am J Med 1999; 107:262-267.
31. Cole TL, Center SA, Flood SN, et al. Diagnostic comparison of needle and wedge biopsy specimens of the liver in dogs and cats. J Am Vet Med Assoc 2002;220:1483-1490.
32. Twedt DC, Diehl KJ, Lappin MR, Getzy DM. Association of hepatic necrosis with trimethoprim sulfonamide administration on 4 dogs. J Vet Intern Med 1997;11:20-23.
33. Rutgers CH, Batt RM, Vaillant C, Riley JE. Subcellular pathologic features of glucocorticoid-induced hepatopathy in dogs. Am J Vet Res 1995;56:898-907.
34. Dorr AT, Soble MJ, Alberts DS. Interaction of cimetidine but not ranitidine with cyclophosphamide in mice. Cancer Res 1986;46: 1795-1799.
35. Volkin RL, Shadduck RK, Winkelstein A, et al. Potentiation of carmustine-cranial irradiation-induced myelosuppression by cimetidine. Arch Intern Med 1982;142:243-245.
36. Hess WA, Kornblith PL. Combination of lomustine and cimetidine in the treatment of a patient with malignant glioblastoma: A case report. Ann Intern Med 1985;69:733.