58° Congresso Nazionale SCIVAC: Oncologia veterinaria

58° Congresso Nazionale SCIVAC • Milano, 7-9 Marzo 2008 • Oncologia veterinaria - Alle soglie del III Millennio
DACARBAZINE
Dacarbazine is one of several imidazole carboxamide derivatives developed
in the mid-1960’s.
Mechanism of action
Dacarbazine inhibits DNA and RNA synthesis by creation of 06-methyguanine
adducts in DNA. Dacarbazine is cell cycle phase nonspecific.
Pharmacokinetics
Dacarbazine is a prodrug and is biotransformed by liver microsomal enzymes.
Active and inactive byproducts may also be created through photodegradation,
thus it should be protected from light. The drug has only modest binding
to plasma proteins and tissues, and excretion is primarily by the kidneys.
It may be administered as an 8-hour infusion or 800 mg/m 2 every 21 days. It
is recommended that dogs be pretreated with dexamethasone through the intravenous
catheter to prevent vasospasm and phlebitis associated with the administration
of this drug. Treatment with butorphanol for injection discomfort
may be helpful for dogs being treated with the 8-hour infusion protocol.
Toxicity
Myelosuppression and gastrointestinal signs can be seen in association
with dacarbazine use. Dacarbazine can be a vascular irritant, and extravasation
can cause severe local tissue reaction.
Indications
Dacarbazine is used to treat malignant melanoma and lymphomas. It has
been used in veterinary medicine as a rescue agent for lymphoma, as well as
for treatment of malignant melanoma and soft tissue sarcomas.
Contraindications
Known hypersensitivity to the drug and myelosuppression prior to administration
are contraindications.
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