58° Congresso Nazionale SCIVAC: Oncologia veterinaria

58° Congresso Nazionale SCIVAC • Milano, 7-9 Marzo 2008 • Oncologia veterinaria - Alle soglie del III Millennio
Mechanism of action
Asparaginase catalyzes the deamination of asparagine to aspartic acid and
ammonia. Asparagine is found incorporated into most proteins and protein
synthesis is halted in its absence with a resulting halt to cellular proliferation.
Drug resistance occurs when cells induce the enzyme asparagines synthetase.
Pharmacokinetics
The usual dose of asparaginase in dogs is 10,000 units/m 2 administered intramuscularly,
subcutaneously, or intraperitoneally. The dose in cats is 400
units/kg body weight. After parenteral administration, asparaginase distributes
into a body space that is only slightly larger than the plasma volume. Little
asparaginase reaches the CSF, but depletion of plasma asparagines results
in decrease of asparagine in CSF. It is believed that the drug is ultimately cleared
by the reticuloendothelial system.
Toxicity
Toxicities associated with asparaginase are unique for an anticancer chemotherapeutic.
Myelosuppression is rare, but may be seen particularly with
concurrent vincristine administration in lymphoma induction. Coagulopathies
and thrombosis have been observed in human patients, presumably as a result
of inhibition of liver protein synthesis. Asparaginase can cause anaphylaxis,
and acute, life-threatening necrotizing pancreatitis is also a rare complication.
Indications
Asparaginase is useful for treatment of acute lymphoblastic leukemia and
lymphoblastic lymphoma in both human and veterinary medicine.
Contraindications
Contraindications include anaphylaxis and pancreatitis.
Address for correspondence:
Barbara E. Kitchell
Professor and Director, Center for Comparative Oncology
Michigan State University College of Veterinary Medicine
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