Page 1301 - Small Animal Internal Medicine, 6th Edition

CHAPTER 76 Practical Chemotherapy 1273

mitoxantrone. The major toxicities of these drugs are myelo-
BOX 76.1 suppression and gastrointestinal; doxorubicin and actinomy-
VetBooks.ir Types of Anticancer Drugs cin D are extremely caustic if given perivascularly, resulting
in severe extravasation injuries. Additionally, doxorubicin
has cumulative cardiotoxic effects in dogs and may cause
Alkylating Agents
Cyclophosphamide renal tubular damage with repeated dosing in cats. Antitu-
Chlorambucil mor antibiotics are listed in Box 76.1.
Melphalan Plant alkaloids are derived from the periwinkle plant
CCNU (lomustine) (Vinca rosea) and the May apple plant (Podophyllum pelta-
Carboplatin tum). Vinca derivatives disrupt the mitotic spindle and are
therefore cell cycle phase-specific (active during M phase),
Antimetabolites whereas Podophyllum derivatives cross-link DNA. The major
Cytosine arabinoside toxicity is perivascular sloughing if the agent extravasates.
Methotrexate
Gemcitabine Although traditionally etoposide was not given intrave-
5-Fluorouracil; SHOULD NOT BE USED IN CATS! nously because the vehicle (Tween 80) causes anaphylaxis, a
Azathioprine recent study in 27 dogs with lymphoma using etoposide
Rabacfosadine phosphate, a water-soluble derivative, reported no cases of
anaphylaxis. Paclitaxel has also been recently used in dogs
Antitumor Antibiotics with neoplasia, primarily carcinomas; however, after condi-
Doxorubicin tional USDA approval for dogs, the drug was taken off the
Bleomycin market. Box 76.1 lists selected plant alkaloids.
Actinomycin D Hormones (corticosteroids) are commonly used for the
Mitoxantrone treatment of hemolymphatic malignancies, mast cell tumors,
Plant Alkaloids and brain tumors (where they result in clinical improvement
Vincristine due to decrease in tumor-associated edema). Box 76.1 lists
Vinblastine the most commonly used hormone.
Vinorelbine Miscellaneous agents consist of drugs with a mechanism
Etoposide or VP-16 of action that is either unknown or differs from those of
Paclitaxel agents already described. Box 76.1 lists miscellaneous agents
commonly used in small animals with cancer.
Hormones A novel approach to anticancer chemotherapy is to exploit
Prednisone the use of inhibitors of molecular targets such as the tyrosine
kinase (TK) family receptors. These include vascular endo-
Miscellaneous Agents thelial growth factor receptor (VEGFR), platelet-derived
L-Asparaginase growth factor receptor (PDGFR), fibroblast growth factor
Rabacfosadine
receptor (FGFR), and Tie1/2, among others. Kit is a receptor
found on mast cells, and Kit signaling is required for the
differentiation, survival, and function of mast cells. Kit
cell cycle phase-nonspecific) and are more active if given mutations are commonly identified in human chronic
intermittently at high doses. The major toxicities of these myelogenous leukemia; imatinib (Gleevec, Novartis, East
drugs are myelosuppression and gastrointestinal. Alkylating Hanover, NJ) selectively blocks this TK pathway and induces
agents commonly used in pets with cancer are listed in apoptosis of neoplastic (but not normal) cells. Mutations of
Box 76.1. Kit are also common in canine mast cell tumors, where other
Antimetabolites exert their activity during the S phase of small molecule TK inhibitors have been effective. Toceranib
the cell cycle (cell cycle phase-specific) and are more active (Palladia, Zoetis, Madison, NJ), masitinib, and imatinib have
if given repeatedly at low doses or as continuous intravenous been used extra-label in small animal patients for a variety
infusions. These drugs are structural analogs of naturally of tumors (despite Palladia being approved for use in mast
occurring metabolites (fake metabolites) that substitute for cell tumors); Palladia was the first FDA-approved drug for
normal purines or pyrimidines. The major toxicities of these canine cancer.
drugs are myelosuppression and gastrointestinal. Box 76.1
lists the antimetabolites commonly used in small animals
with cancer. METRONOMIC CHEMOTHERAPY
Antitumor antibiotics act by several mechanisms (i.e.,
cell cycle phase-nonspecific), the most important of which After Judah Folkman discovered tumor angiogenesis, several
appears to be DNA damage produced by free radicals or groups proposed that anticancer drugs may be able to target
by a topoisomerase-II–dependent mechanism. There are tumor vasculature because many of the endothelial cells that
now several synthetic or semisynthetic antibiotics, such as compose the wall of tumor blood vessels are immature