Vascular access ports
For systemic chemotherapeutic protocols to be effective, the adequate and consistent delivery of antineoplastic agents is
required. Because many dogs are food-motivated, oral chemotherapeutic drugs are generally easy to administer. However, some
of the most effective chemotherapeutic agents, such as doxorubicin, are available principally as intravenous formulations.
Unlike oral drugs in which bioavailability may be of concern, known quantities of intravenous chemotherapeutic agents can
be reliably administered. Although intravenous chemotherapy avoids the unpredictable absorption profiles of oral drugs, some
intravenous anticancer agents are irritants or vesicants and can cause marked regional pain and tissue damage when extravasated.
Severe tissue necrosis secondary to extravasation of doxorubicin may require surgical débridement and, occasionally, amputation
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.
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.