58° Congresso Nazionale SCIVAC: Oncologia veterinaria

58° Congresso Nazionale SCIVAC • Milano, 7-9 Marzo 2008 • Oncologia veterinaria - Alle soglie del III Millennio
Pharmacokinetics
Lomustine is administered orally. The standard dose used in small animals
ranges from 50 mg/m 2 to 90 mg/m 2 PO on a 3-week basis. Dose for cats has
been reported at 60 mg/m 2 PO or as a 10 mg dose per cat every 3 weeks. Lomustine
is widely distributed because of its lipid solubility. It penetrates the
blood-brain barrier and CSF levels are 15-50% of plasma. Lomustine is extensively
metabolized in the liver to both inactive and active metabolites. The
half-life of the active metabolites ranges from 16 hours to 2 days. Lomustine’s
active and inactive metabolites are excreted primarily in the urine. Prolongation
of plasma concentration is thought to reflect a combination of protein
binding and enterohepatic recirculation of metabolites.
Toxicity
The major toxic effect of lomustine therapy is acute and delayed (4-6 weeks
post dosing) bone marrow suppression (especially thrombocytopenia and leukopenia).
It is recommended that the practitioner monitor the CBC one week after
dosing, and again immediately before the next dose is scheduled. Myelosuppression
can occur for up to 6 weeks after dosing. Nausea and vomiting are rarely
seen with lomustine use. Hepatic toxicity has been described in dogs. While
most of the hepatic toxicity seen was manifested as reversible elevation of liver
enzymes, a small percentage of dogs had progressive, fatal hepatic failure.
Indications
Veterinary indications include the treatment of refractory lymphosarcoma
in dogs and cats, metastatic mast cell disease in dogs and cats, cutaneous
lymphosarcomas, and central nervous system tumors.
Contraindications
Use with caution in dogs treated with drugs that need microsomal enzyme
induction (ie phenobarbital) due to the possible changes in antineoplastic activity.
Combination with other myelosuppressive drugs should be carefully
monitored. Lomustine has been demonstrated to induce significant and even
fatal hepatic toxicity in a limited number of canine patients; its use is therefore
contraindicated in patients with pre-existing clinical hepatic dysfunction.
Use should be discontinued in the face of elevating liver enzyme levels.
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