58Â° Congresso Nazionale SCIVAC: Oncologia veterinaria

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58° Congresso Nazionale SCIVAC • Milano, 7-9 Marzo 2008 • Oncologia veterinaria - Alle soglie del III Millennio therapy for transmissible venereal tumors. Because vincristine can induce thrombocytosis it may also be employed in the treatment of immune-mediated thrombocytopenia. Contraindications Should be used with caution in patients with hepatic disease, leukopenia, infection, or preexisting neuromuscular disease. VINBLASTINE Vinblastine has essentially the same mechanism of action as vincristine. Pharmacokinetics Vinblastine is administered intravenously, at a dose of 2 mg/m 2 body surface area. Vinblastine binds extensively to blood and other cellular elements. The drug is metabolized in part in the liver to another active compound, deacetylvinblastine and is excreted primarily in bile. Toxicity Adverse reactions to vinblastine are dose related and reversible. Toxicity may be enhanced by the presence of hepatic insufficiency. Leukopenia is usually dose limiting. Nausea and vomiting are the most frequent adverse GI effects, and usually last less than 24 hours. Neurotoxicity is less frequently encountered than with vincristine. Tissue irritation, phlebitis and necrosis can result from extravasation. Indications Vinblastine is used for treatment of mast cell disease in dogs and cats, as well as for rescue therapy in lymphosarcoma. Contraindications Known hypersensitivity, and significant liver dysfunction are contraindications. 64
58° Congresso Nazionale SCIVAC • Milano, 7-9 Marzo 2008 • Oncologia veterinaria - Alle soglie del III Millennio TOPOISOMERASE INHIBITORS Are drugs that interact with the physical structure and activity of DNA both in the production of RNA and replication of DNA. These drugs are typically natural products that inhibit the DNA unwinding enzyme topoisomerase. DOXORUBICIN Doxorubicin was discovered in Italy as an anthracycline antibiotic derivative of a soil fungus. Mechanism of action Doxorubicin is a particularly potent antineoplastic drug in part because it has several different actions that can result in cell death. Doxorubicin intercalates DNA, and by virtue of the presence of quinone and hydroquinone side chains can for covalent cross-links. The presence of doxorubicin in the DNA chain impairs DNA synthesis, RNA synthesis, topoisomerase activity, and helicase activity. Doxorubicin is capable of causing iron-mediated free-radical formation, which in turn leads to lipid peroxidation and cell membrane effects. Mechanism of drug resistance is largely through activation of the P- glycoprotein cell membrane pump. P-glycoprotein activity results in inability of the doxorubicin to insert itself into nuclear DNA. Pharmacokinetics Doxorubicin is administered intravenously at doses of 30 mg/m 2 body surface area in dogs or 1 mg/kg dose in cats and small dogs. Doxorubicin undergoes extensive biotransformation in the liver to active and inactive metabolites. The drugs is extensively protein abound in plasma and tissues and is excreted almost exclusively in bile in animal species. Toxicity In addition to having the broadest spectrum of activity of any of the commonly used antineoplastic drugs, doxorubicin also has perhaps the widest profile of commonly seen significant toxicities. Myelosuppression, gastrointestinal signs (particulary nausea, vomiting and colitis), and alopecia are all seen in pa- 65
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58Â° Congresso Nazionale SCIVAC: Oncologia veterinaria

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