Vascular access ports

FIGURE 5. Severe tissue necrosis of the antebrachium requiring surgical intervention in a rottweiler two weeks after perivenous extravasation of doxorubicin.

To minimize the likelihood of chemotherapy extravasation, ensure that intravenous catheters are properly placed and firmly secured before chemotherapy administration. In patients in which intravenous catheter placement is difficult, such as markedly obese patients or those with anatomical variations, vascular access ports surgically implanted in the jugular vein may provide a reliable means for repeated intravenous therapy over weeks to months. Vascular access ports are becoming more common in veterinary medicine for the management of both diabetic and cancer patients. Vascular access ports specifically designed for companion animals of various body sizes are available (e.g. Companion Port—Norfolk Vet Products, Skokie, Ill.), and their use should be considered in circumstances in which intravenous access is difficult or when repeated and long-term vascular access is necessary.

Corticosteroids cause normal lymphocytes to undergo programmed cell death.¹⁴ Similarly, corticosteroids induce cytolytic effects in lymphoid malignancies such as canine lymphoma. Because of their lympholytic properties, corticosteroids such as oral prednisone exert therapeutic effects and can be used to treat canine lymphoma. Given prednisone's low cost, oral formulation, and predictable and familiar side effect profile, veterinary practitioners may be inclined to use single-agent oral prednisone to treat canine lymphoma. About 50% of dogs with high-grade, multicentric lymphoma treated with single-agent prednisone may achieve clinical responses for one to three months. However, the single-agent use of oral prednisone should only be instituted if pet owners, who have been educated of their therapeutic options, actively choose not to pursue superior multiagent chemotherapeutic protocols. Additionally, be aware that the use of oral prednisone before the definitive diagnosis of lymphoma may reduce the efficacy of traditional antineoplastic agents for treating canine lymphoma through the up-regulation of resistance mechanisms.

Multidrug-resistant phenotype is a term used to describe neoplastic cells that are resistant to the cytotoxic effects of certain antineoplastic agents. In dogs with lymphoma, acquired drug resistance has been classically associated with the expression of a drug efflux pump termed P-glycoprotein (Pgp). Functionally, Pgp prevents the retention of cytotoxic agents such as doxorubicin and vincristine within lymphoma cells, allowing malignant lymphocytes to escape lethal DNA injury. Glucocorticoids have been demonstrated to up-regulate Pgp expression in malignant lymphocytes.¹⁵ For this reason, treating canine lymphoma with single-agent prednisone should be discouraged, as the net effect may be the promotion of malignant lymphocytes resistant to conventional antineoplastic agents.

Oral lomustine

Lomustine, (CeeNU—Bristol Laboratories) is classified as an antitumor alkylating agent in the nitrosourea family. Lomustine is available in 10-, 40-, and 100-mg capsules. After oral administration, lomustine undergoes hepatic metabolism, and unchanged parent drug and biotransformed metabolites are ultimately eliminated through the kidneys, with biliary excretion and reabsorption from the gut also playing a chief role.¹⁶

The safety and efficacy of single-agent lomustine has been evaluated for treating canine lymphoma. Forty-three dogs with lymphoma that had relapsed or had failed to achieve complete remission with previous conventional chemotherapy were treated with single-agent lomustine every 21 days at a dose of 90 to 100 mg/m². Of the dogs treated, 28% achieved either complete or partial responses for a median duration of 86 days. The principal side effects associated with lomustine administration were hematologic; acute self-limiting neutropenia and cumulative thrombocytopenia occurred in dogs receiving continued long-term lomustine therapy.¹⁷

Although hematologic toxicosis was recognized as a self-limiting adverse effect of lomustine therapy in dogs with refractory lymphoma, a more recent study incriminates lomustine as being hepatotoxic in cancer-bearing dogs. In this study, 179 dogs received lomustine for the treatment of various cancer types including lymphoma. After lomustine therapy, hepatotoxicity was identified in a few patients (6.1%).¹⁸ Dogs receiving a higher number of doses and higher cumulative doses were more likely to develop hepatotoxicity. Most of the dogs with hepatotoxicity were euthanized as a direct consequence of liver failure. The findings from this study suggest that lomustine, although considered an effective chemotherapeutic agent for treating various cancer types, may induce a delayed, cumulative dose-related, chronic hepatotoxicity that is irreversible and often fatal.