58° Congresso Nazionale SCIVAC: Oncologia veterinaria
58° Congresso Nazionale SCIVAC: Oncologia veterinaria
58° Congresso Nazionale SCIVAC: Oncologia veterinaria
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58° <strong>Congresso</strong> <strong>Nazionale</strong> <strong>SCIVAC</strong> • Milano, 7-9 Marzo 2008 • <strong>Oncologia</strong> <strong>veterinaria</strong> - Alle soglie del III Millennio<br />
Pharmacokinetics<br />
Dacarbazine is a prodrug and is biotransformed by liver microsomal<br />
enzymes into MTIC. Temozolamide does not require hepatic enzyme activation<br />
and therefore has a more predictable pharmacologic profile than dacarbazine.<br />
The drug has minimal binding to plasma proteins and tissues, and<br />
the half life of the active compound is 1.8 hours. The drug is spontaneously<br />
degraded in the body to inactive compound, so elimination is not a concern<br />
for this agent. The drug depletes the DNA repair enzyme 0-6 alkylguanyl<br />
alkyltransferase, which means that over the course of 5 days of drug administration<br />
every 21 days, the pills at the end of the 5 day administration<br />
cycle have more profound effect than those administered initially. As the<br />
agent causes DNA injury, the repair enzyme is depleted to late injuries are<br />
more damaging to the cancer cells as well as to normal replicating cells in<br />
the marrow.<br />
Toxicity<br />
Myelosuppression and gastrointestinal signs can be seen in association<br />
with temozolomide use. The drug is best absorbed on an empty stomach, but<br />
it is a gastric irritant. Thus it is recommended that the patient be fasted for<br />
at least one hour prior to drug administration, then fed in 20-30 minutes.<br />
Metaclopromide is helpful as an antiemetic. If the capsules are chewed by<br />
the dog, the drug can act as a mucosal irritant to care must be taken when<br />
pilling dogs. In cats, we have observed apparent cardiac adverse effects and<br />
pleural effusion in 20% of cats treated. We are currently not recommending<br />
this drug for use in cats until further study to predict the risk of significant<br />
toxicity is completed.<br />
Indications<br />
Temozolomide has been used to treat malignant melanoma and lymphomas<br />
in the dog, and has shown some effect in combination with doxorubicin<br />
and vincristine to treat hemangiosarcoma.<br />
Contraindications<br />
Known hypersensitivity to the drug and myelosuppression prior to administration<br />
are contraindications.<br />
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