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Lomustine is a chemotherapeutic-alkylating agent. It
is also commonly 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 rapidly absorbed
from the GI tract. In order to decrease nausea, lomustine should be given
on an empty stomach. There is some topical absorption of lomustine.
Lomustine is commonly used 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 percent to 50 percent 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 is also used in relapsing lymphosarcoma in cats.
Lomustine is used as a first-line drug in the treatment of cutaneous lymphoma of dogs with a response rate of 80 to 90 percent and 26 percent 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 is usually 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 percent. Lomustine was found to not 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 is also a favorable report of the use of lomustine within
a multiple-drug protocol for the treatment of optic neuritis secondary
to granulomatous meningoencephalomelitis.
• Side effects include bone-marrow suppression,
including anemia thrombocytopenia, and leucopenia. Approximately 40 percent
of treated dogs will have neutrophil counts of less than 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 may also be experienced.
• Animals with anemia, bone-marrow depression,
decreased pulmonary function, infection and decreased liver and kidney
function should only receive lomustine when the benefits outweigh the
potential risks.
• The occurrence of neutropenia is a dose-limiting factor for lomustine.
The nadir for thrombocytopenia and neutropenia is usually at 7 to 10 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.
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 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
To help protect veterinary staff and patients from unnecessary exposure to chemotherapy medications and waste, this handling sheet will be included with all chemotherapy prescriptions we dispense.
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risks and benefits of using a particular product. You should consult your doctor
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