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Lomustine for Veterinary Use
by Barbara Forney, VMD
Lomustine is a chemotherapeutic alkylating agent. It also commonly is referred to as CCNU. Alkylating agents disrupt DNA transcription and RNA replication. They are not cell stage specific. Lomustine is metabolized in the liver and excreted in the kidneys. It is highly lipid soluble and crosses the blood-brain barrier into the CNS. Lomustine is absorbed rapidly from the GI tract. In order to decrease nausea, lomustine should be given on an empty stomach. There is some topical absorption of lomustine.
Dogs and Cats
Lomustine is used commonly and considered efficacious in rescue protocols for relapsed canine lymphoma. Numbers regarding remission vary but complete or partial remission may be achieved in as many as 25%-50% of dogs with drug resistant lymphoma. Results with the use of lomustine as a first line treatment for canine lymphoma are less promising, although it may be used as a first line treatment when finances and or owner compliance limit the treatment options. Lomustine also is used in relapsing lymphosarcoma in cats.
Lomustine is used as a first line drug to treat cutaneous lymphoma of dogs with a response rate of 80-90% and 26% achieving complete remission. The duration of treatment to response is reported to be about three to four months.
Lomustine is helpful for chemotherapy of mast cell tumors in both dogs and cats. Complete surgical removal is the most effective treatment for canine mast cell tumors; multiple authors emphasize the importance of clean margins. In tumors that are not completely resectable due to location or size, radiation and chemotherapy have both proved useful. Chemotherapy usually is used in tumors that are grade II or above. Lomustine is safe to use with prednisone and has provided complete or partial remission in a number of cases. One study gave the overall response rate in cats with mast cell tumors as 50%. Lomustine was found not to be beneficial in dogs with advanced mast cell tumors that had bone marrow involvement.
The most common primary intracranial tumor of dogs is astrocytoma (glial cell tumor). Because active metabolites of lomustine are found in the CSF it has been used in the palliative treatment of intracranial tumors. There also is a favorable report of the use of lomustine within a multiple drug protocol to treat optic neuritis secondary to granulomatous meningoencephalomelitis.
Lomustine Side Effects
Side effects include bone marrow suppression, including anemia thrombocytopenia and leucopenia. Approximately 40% of treated dogs will have neutrophil counts of <1,000 cells/uL at seven days after treatment. GI effects can include vomiting, anorexia and diarrhea. Hepatotoxicosis, alopecia, corneal de-epithelization and renal and pulmonary damage also may be experienced.
- Animals with anemia, bone marrow depression, decreased pulmonary function, infection and decreased liver and kidney function should receive lomustine only when the benefits outweigh the potential risks.
- The occurrence of neutropenia is a dose limiting factor for lomustine. The nadir for thrombocytopenia and neutropenia usually is at seven to ten days post therapy. Hematologic changes may be delayed and cumulative, although more commonly they are resolved before the next treatment. Platelet counts should be performed before each treatment.
- Lomustine can cause chronic irreversible liver failure in dogs. Liver enzymes should be evaluated prior to each treatment. Manifestation of hepatotoxicity may be delayed by as long as four weeks after cessation of treatment. Hepatotoxicity has not been reported in cats.
- Because Lomustine is excreted by the kidneys, dose modification may be needed in animals with pre-existing renal disease. Glucosuria may be an early sign of renal tubular damage.
- Lomustine should be used with caution with other myelosuppressive or immunosuppressive drugs due to additive bone marrow suppression or increased risk of infection.
- Vaccination with live virus vaccines should be avoided in animals receiving lomustine.
Lomustine has a narrow effective dose range prior to toxicity. Overdose should be treated aggressively with gut emptying protocols.
About the Author
Dr. Barbara Forney is a veterinary practitioner in Chester County, Pennsylvania. She has a master's degree in animal science from the University of Delaware and graduated from the University of Pennsylvania School of Veterinary Medicine in 1982.
She began to develop her interest in client education and medical writing in 1997. Recent publications include portions of The Pill Book Guide to Medication for Your Dog and Cat, and most recently Understanding Equine Medications published by the Bloodhorse.
Dr. Forney is an FEI veterinarian and an active member of the AAEP, AVMA, and AMWA.
You can purchase books by Dr. Forney at www.exclusivelyequine.com
Wedgewood Pharmacy's compounded veterinary preparations are not intended for use in food and food-producing animals.