Douglas H. Thamm
Key points
· Chemotherapy is the only form of cancer therapy that treats the entire body.
· Chemotherapy drugs are classified according to their mechanism of action, and if they interfere with cellular reproduction.
· Cell-cycle phase specific
· Cell-cycle phase nonspecific
· Combining cytotoxic drugs is an effective strategy.
· Reduces drug resistance
· Knowing the route of administration (“routes”), rate of administration (“duration”), and specific contraindications (“special precautions”) are key factors for success.
Introduction
Unlike surgery and radiation therapy, chemotherapy is the only form of cancer treatment that can work throughout the body, rather than in a local area. Although chemotherapy in animals is designed to have a lower risk of side effects than chemotherapy in humans, side effects can be seen in some patients. Educating owners about the risks of side effects is an important part of chemotherapy in pets (see Chapters 1 and 8 for additional information).
Although other chapters in this book cover owner education, pretreatment assessment, administration techniques, and strategies for managing side effects, the purpose of this chapter is to provide a quick reference regarding individual chemotherapy drugs—their uses, toxicities, and routes and techniques for administration. For detailed information about doses and schedules of administration, additional references are provided at the end of this chapter.
Chemotherapy drugs are classified according to their mechanism of action and the point in the cell’s life cycle at which they interfere with cellular reproduction. Drugs that are active only during a specific phase of the cell’s life cycle are called cell-cycle phase specific. Drugs that are active regardless of the cell’s life cycle phase are called cell-cycle phase nonspecific. The use of cell-cycle phase-nonspecific drugs appears to result in the death of both resting and cycling cells. Following cell death, resting cells are “awakened” into the reproduction cycle and are then more susceptible to future chemotherapy treatments. The awakened cell will then die as it attempts to reproduce itself. The cell kill rate of various drugs is related to the concentration of the drug in the body and to the degree of tumor cell exposure over time.
Combining cytotoxic drugs is an important, effective strategy in chemotherapy. When drugs are used in combination, they often enhance the activities of each other. Drugs are also combined to minimize their dose-limiting toxicities. Combination drug chemotherapy also helps reduce the development of drug resistance in the tumor cells, since cells resistant to one drug in a combination may be sensitive to another drug within that combination.
Treatment dose and schedule depend on the type of cancer and chemotherapy method. In many cases, periodic chemotherapy is necessary to control the cancer for the rest of the pet’s life. For maximum therapeutic effect, a dose of a drug or a drug combination should be used, which causes minimal toxicity with maximal effectiveness. Many chemotherapy drugs have a very narrow therapeutic index. This means that the most effective dose of chemotherapeutic agents is often very close to the toxic dose.
For the information below, the risk for neutropenia and gastrointestinal (GI) toxicity are graded on a 3-point scale (0, +, ++), where “0” is rare and “++” is more common. It is important to note that even for those drugs where the risk is “++,” less than one third of animals become sick.
Actinomycin D
Other names: dactinomycin, Cosmegen
Uses: Canine (rarely feline) lymphoma
Routes: intravenous (IV) only!
Duration: 2- to 5-minute slow push. Can be diluted with sodium chloride before administration.
Toxicities: Neutropenia: +/++ GI toxicity: +
Special precautions:
· Can cause severe tissue damage if even a slight amount is administered outside the vein.
Asparaginase
Other names: Elspar, L-spar
Uses: Used with other drugs for the treatment of canine and feline lymphomas and leukemias.
Routes: subcutaneous (SQ) or intramuscular (IM). Should never be given intravenously!
Duration: Bolus
Toxicities: Neutropenia: 0 GI toxicity: 0
Special precautions:
· Hypersensitivity reactions can occur following administration. These can be fatal if the asparaginase is given intravenously. Patient should be monitored in the clinic for 60 minutes after injection.
Carboplatin
Other names: Paraplatin
Uses: Canine and feline carcinomas and melanomas, canine osteosarcoma, feline vaccine-associated sarcoma
Routes: IV; occasionally given intralesionally (directly into a tumor) or into a body cavity
Duration: 5- to 10-minute slow push
Toxicities: Neutropenia: ++ GI toxicity: 0/+
Special precautions:
· Use with caution in patients with reduced kidney function.
· Smaller dogs may be at increased risk for diarrhea.
Chlorambucil
Other names: Leukeran
Uses: Chronic lymphocytic leukemia and low-grade lymphomas in dogs and cats. Occasionally used for lymphomas in place of cyclophosphamide.
Routes: per os (PO) only
Toxicities: Neutropenia: + GI toxicity: 0/+
Special precautions:
· Thrombocytopenia (low platelet count) can sometimes be observed with long-term use.
Cisplatin
Other names: Platinol, CDDP
Uses: Canine osteosarcoma and various carcinomas
Routes: IV; occasionally given intralesionally (directly into a tumor) or into a body cavity.
Duration: 20-minute infusion. Must be given along with high rates of IV fluid diuresis before and after administration.
Toxicities: Neutropenia: + GI toxicity: ++
Special precautions:
· Can cause severe kidney damage if not given with high rates of IV fluid diuresis before and after administration. Check kidney function before each dose.
· Vomiting or severe nausea is common immediately after administration. Patients need to receive antinausea drugs before cisplatin is given to prevent this.
· Fatal to cats! Do not use in this species!
Cyclophosphamide
Other names: Cytoxan
Uses: Used with other drugs (doxorubicin, vincristine, asparaginase) for the treatment of canine and feline lymphomas. Sometimes used for the treatment of sarcomas in combination with doxorubicin. Can also be used as an immunosuppressive drug in dogs and cats.
Routes: IV and PO
Duration: 3- to 5-minute slow push (IV)
Toxicities: Neutropenia: + GI toxicity: +
Special precautions:
· Sterile hemorrhagic cystitis (an irritation of the bladder causing signs similar to a urinary tract infection) can occur rarely. Cyclophosphamide is often given along with the diuretic drug furosemide (Lasix) to dilute the urine and encourage excretion of the by-product that irritates the bladder.
Cytarabine
Other names: cytosine arabinoside, Cytosar, AraC
Uses: Canine and feline lymphomas: Occasionally used for the treatment of granulomatous meningoencephalitis in dogs.
Routes: IV and SQ
Duration: 30-minute to 24-hour infusion (IV)
Toxicities: Neutropenia: + GI toxicity: +
Special precautions:
· A poorly placed SQ injection creates the opportunity for accidental drug spill, errant injection, and needlestick injury.
Doxorubicin
Other names: Adriamycin
Uses: Canine and feline lymphomas, leukemias, carcinomas, and sarcomas including osteosarcomas and hemangiosarcomas.
Routes: IV only!
Duration: 10- to 20-minute IV infusion or slow push. Often diluted in sodium chloride before administration.
Toxicities: Neutropenia: ++ GI toxicity: ++
Special precautions:
· Can cause severe tissue damage if even a slight amount is administered outside the vein.
· Hypersensitivity reactions can occur during administration. Monitor patients for reddening of mucous membranes/skin, head shaking, facial swelling, or hives during administration.
· Damage to the heart can occur in dogs if more than six doses are administered.
· Damage to the kidneys can occur in cats if with multiple doses. Check kidney function in cats prior to each treatment.
Lomustine
Other names: CCNU, CeeNu
Uses: Canine and feline lymphomas, mast cell tumor, histiocytic sarcomas, occasionally brain tumors
Routes: PO only
Toxicities: Neutropenia: +/++ GI toxicity: 0/+
Special precautions:
· Thrombocytopenia (low platelet count) can sometimes be observed with long-term use.
· Elevations in liver enzymes can be observed with long-term use. Liver values should be checked before each treatment.
Melphalan
Other names: Alkeran
Uses: Canine and feline multiple myelomas. Occasionally used for lymphomas.
Routes: PO only in veterinary medicine
Toxicities: Neutropenia: + GI toxicity: 0/+
Special precautions:
· Thrombocytopenia (low platelet count) can sometimes be observed with long-term use.
Mitoxantrone
Other names: Novantrone
Uses: Canine and feline lymphomas, bladder tumors, anal sac tumors
Routes: IV; occasionally given into a body cavity
Duration: 10- to 20-minute infusion or slow push. Dilute with sodium chloride before administration.
Toxicities: Neutropenia: +/++ GI toxicity: 0/+
Special precautions:
· Mild tissue damage can occur if given outside a vein
Vinblastine
Other names: Velban
Uses: Canine and feline mast cell tumors; occasionally used for lymphomas.
Routes: IV only!
Duration: 1- to 2-minute push
Toxicities: Neutropenia: +/++ GI toxicity: 0/+
Special precautions:
· Moderate tissue damage can occur if given outside a vein
Vincristine
Other names: Oncovin
Uses: Canine and feline lymphomas, transmissible venereal tumor. Sometimes used in combination with cyclophosphamide and doxorubicin for the treatment of canine sarcomas. Can also be used to help increase platelet count in dogs with immune-mediated thrombocytopenia.
Routes: IV only!
Duration: 20-second to 1-minute push
Toxicities: Neutropenia: + GI toxicity: 0/+
Special precautions:
· Moderate tissue damage can occur if given outside a vein
Additional Reading
Chun R, Garrett LD, Vail DM. 2007. Cancer chemotherapy. In: Withrow SJ, Vail DM (eds.), Small Animal Clinical Oncology (4th Ed.). St. Louis, MO: Saunders Elsevier, pp. 163–92.
Moore AS, Frimberger AE. 2009. Anticancer drugs and protocols: Traditional drugs. In: Bonagura JA, Twedt DC (eds.), Kirk’s Current Veterinary Therapy XIV. St. Louis, MO: Saunders Elsevier, pp. 305–10.
Plumb DC. 2008. Plumb’s Veterinary Drug Handbook. Hoboken, NJ: Wiley-Blackwell.