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 tients treated with doxorubicin. In addition, anaphylaxis and urticarial reactions may be seen that can be dependent on rate of infusion and can be blocked by premedication with antihistamines and corticosteroids. Extravasation of the drug can result in severe tissue necrosis that can necessitate reconstructive surgery. Intravenous injection without extravasation can cause thrombophlebitis and venous sclerosis. Cardiac toxicity is dose limiting, and can be seen in acute and chronic forms. Acute cardiac toxicity results in arrhythmias, ST-T wave changes, sinus tachycardia, and extrasystolic contractions. Pretreatment cardiac assessment is indicated for dogs receiving doxorubicin therapy. Chronic cumulative cardiac toxicity is characterized by a progressing syndrome of congestive heart failure. Risk increases with increasing cumulative dose, typically in the range of 180-240 mg/m 2 in dogs. Caution should always be exercised as cardiotoxicity may occur at much lower cumulative doses in patients with preexisting heart disease. Dexrazoxane partially prevents anthracycline-induced cardiotoxicity by chelating free iron and preventing the formation of the anthracycline iron complex and resultant free radical generation. Cats are also susceptible to renal toxicity that can result in acute or acute on chronic renal failure. Indications Doxorubicin has one of the widest spectrums of activity of any of the anticancer agents, and is used for treatment of leukemias, lymphoma, sarcomas, and carcinomas. Contraindications Known hypersensitivity, preexisting cardiac disease, preexisting renal insufficiency in cats. MITOXANTRONE Mitoxantrone was developed as a synthetic aminoanthraquinone that was hoped to retain the antitumor spectrum of an anthracycline without causing cardiotoxicity. Mechanism of action As for doxorubicin, with the exception that mitoxantrone causes minimal free radical formation and lipid peroxidation. 66
58° Congresso Nazionale SCIVAC • Milano, 7-9 Marzo 2008 • Oncologia veterinaria - Alle soglie del III Millennio Pharmacokinetics Mitoxantrone is administered by IV infusion at doses of 5.0-6.0 mg/m 2 body surface area in dogs and cats. The drug is 78% bound to plasma proteins. The metabolism of mitoxantrone is not well known but is believed to be similar to that seen for other agents in the class. Elimination is also not well know, but 11% is recovered in urine over 5 days, and 25% recovered in feces over 5 days. No adjustment for renal or hepatic dysfunction is recommended. Toxicity Myelosuppression is the main dose limiting toxicity of mitoxantrone. Indications Mitoxantrone is used to treat lymphoma in dogs and cats, and has also been used to treat a variety of solid tumors including transitional cell carcinoma of the urinary bladder, squamous cell carcinoma, mammary carcinoma, and anal sac carcinoma. Contraindications Known hypersensitivity. Mitoxantrone should not be given during pregnancy as it is a teratogen. MISCELLANEOUS AGENTS A variety of different drugs with anticancer activity are classed as miscellaneous agents based on varied mechanisms of action, including hormones, receptor binding agents, and drugs with unique effects. ASPARAGINASE (also called L-asparaginase) Asparaginase is a high molecular weight enzyme extracted from bacteria, primarily Escherichia coli. It was originally discovered in 1953 as an antitumor activity in guinea pig serum that inhibited rodent tumors in cell culture. 67
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58Â° Congresso Nazionale SCIVAC: Oncologia veterinaria

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