Page 1304 - Small Animal Internal Medicine, 6th Edition

1276 PART XII Oncology

CHAPTER 77
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Complications of Cancer

Chemotherapy

GENERAL CONSIDERATIONS In general, cats appear to be more susceptible than dogs
to some of the adverse effects of chemotherapy (e.g., anorexia,
Because most anticancer agents are relatively nonselective, vomiting) but not to others (e.g., myelosuppression). Certain
they kill not only rapidly dividing neoplastic cells but also breeds of dogs, including Collies and Collie crosses, Old
some of the rapidly dividing normal cells in the host (e.g., English Sheepdogs, Cocker Spaniels, and West Highland
villus epithelium, bone marrow cells). In addition, similar to White Terriers, also appear to be more prone to some of the
other commonly used agents (e.g., digitalis glycosides), most acute adverse reactions to chemotherapy (i.e., gastrointestinal
anticancer agents have low therapeutic indices (i.e., narrow signs, myelosuppression) than the general dog population.
therapeutic-to-toxic ratios). Interestingly, only some of these breeds (e.g., Collie, Sheltie)
Because anticancer agents follow first-order kinetic prin- have mutations of the ABCB1 (formerly MDR1) gene that
ciples (i.e., the fraction of cells killed is directly proportional encodes for P-glycoprotein, an efflux pump that rapidly
to the dose used), increasing the dose of a particular drug eliminates chemotherapeutic agents from the cytoplasm of
increases the proportion of the neoplastic cells killed, but it the cells, so alternative mechanisms of toxicity must be
also enhances its toxicity. This is commonly seen when a sought.
tumor relapses and higher doses of a previously prescribed The overall prevalence of toxicity of different chemother-
chemotherapeutic agent are administered. apy protocols is considerably lower in dogs and cats (≈5%-
Because toxicity generally tends to affect rapidly dividing 40%) than in humans (75%-100%) treated with similar drugs
cells, given the short doubling times of the bone marrow and or combinations. A survey of owners whose pets had been
villal epithelial cells, myelosuppression and gastrointestinal treated with a variety of chemotherapy protocols at The Ohio
signs are the most common toxicities encountered in prac- State University Veterinary Medical Center revealed that
tice. Other rare complications of chemotherapy include more than 80% considered their pets’ quality of life to be as
anaphylactoid (or anaphylactic) reactions, dermatologic good as or better than that before the institution of chemo-
toxicity, pancreatitis, cardiotoxicity, pulmonary toxicity, therapy. Additionally, a similar study performed at North
neurotoxicity, hepatopathies, and urotoxicity. Table 77.1 Carolina State University revealed that 77% of dogs and 66%
lists anticancer drugs commonly used in small animals and of cats experienced no negative impact on their quality of life
their toxicities. while undergoing chemotherapy, and 65% of dogs and 44%
Several factors can potentiate the effects of anticancer of cats handled chemotherapy better than the owners were
agents and thereby enhance their toxicity. For example, expecting.
drugs that are excreted primarily through the kidneys (e.g., Recently, the Veterinary Cooperative Oncology Group
platinum compounds, methotrexate) are more toxic to updated the terminology for adverse events after chemo-
animals with renal disease; thus a dose reduction or the use therapy in dogs and cats (Table 77.2).
of an alternative drug is usually recommended in such
patients.
In addition to the direct effects of some drugs on different HEMATOLOGIC TOXICITY
organ systems, rapid killing of certain neoplastic cells (i.e.,
lymphoma cells) can lead to sudden metabolic derangements The high mitotic rate and growth fraction (i.e., 40%-60%) of
that result in acute clinical signs mimicking those of drug the bone marrow cells predispose this organ to relevant tox-
toxicity (i.e., depression, vomiting, diarrhea). This syndrome icity from anticancer drugs. Hematologic toxicity constitutes
is referred to as acute tumor lysis syndrome (ATLS) (see p. the most common complication of chemotherapy, and often
1286) and is extremely rare. the severe and potentially life-threatening cytopenias that

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