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Cyclophosphamide is an alkylating, cytotoxic, anti-neoplastic drug that is used as a part of many of the combination chemotherapies for lymphoma, soft tissue sarcoma and some mammary neoplasia in both dogs and cats. It is also used in the treatment of a variety of immune-mediated diseases. Alkylating drugs form covalent bonds with nucleic acids, causing disruption of DNA replication, RNA transcription and nucleic-acid function. Cyclophosphamide is also a powerful immunosuppressant that affects both B and T lymphocytes. Cyclophosphamide is well-absorbed orally. It is metabolized by the liver and excreted in the urine.
Cyclophosphamide is a pro-drug that is metabolized by
the liver to produce phosphoramide mustard, the active metabolite, and
arcolein, which is a metabolite responsible for one of the major toxicities
associated with this drug (sterile-hemorrhagic cystitis).
Cyclophosphamide is used in both dogs and cats as a part of the multi-drug induction protocol in the treatment of lymphoma. Perhaps the most common use is within the COP protocol (cyclophosphamide, vincristine and prednisone) and the COAP protocol (as above with the addition of cytosine arabinoside). These induction protocols have a relatively low incidence of toxicity (<15 to 20 percent) and compliance is relatively easy. There is a large body of literature and research on the treatment of both canine and feline lymphomas. This disease has proved to be treatable and protocols change and are modified regularly as new information becomes available.
Cyclophosphamide has been used in the treatment of immune-mediated diseases such as: polyarthritis, glomerulonephritis, feline infectious peritonitis, noninfectious inflammatory pulmonary parenchymal disease, neutrophilic vasculitis of Shar Peis and chronic inflammatory polyneuropathy. Cyclophosphamide is no longer used with prednisone in the treatment of acute immune-mediated hemolytic anemia, as recent research has shown that prednisone alone is as or more effective. Cyclophosphamide does not result in more rapid resolution of hemolysis.
Recent research suggests that the co-administration
of furosemide will decrease the side effect of cyclophosphamide-induced
cystitis (CIC). Giving cyclophosphamide in the morning, keeping the patient
well-hydrated and encouraging/allowing them to urinate frequently is also
recommended.
• Myelosuppression is the dose-limiting side effect. Neutropenia occurs 5 to 14 days after administration and usually resolves quickly, although it may take as long as four weeks. Thrombocytopenia is rare. GI side effects may include nausea, vomiting, diarrhea and anorexia. Anorexia is more prominent in cats.
Alopecia may be a side effect among dogs, especially breeds with continuous hair growth such as Poodles or Bichon Frisee. Cats are less likely to develop alopecia but may lose their whiskers.
Bladder toxicity may occur in both dogs and cats. Sterile-hemorrhagic
cystitis may occur due to the effects of the metabolite arcolein on bladder
urothelium.
• Cyclophosphamide should be used with caution
in animals with leukopenia, thrombocytopenia, increased risk of infection
and decreased liver or kidney function.
• Cyclophosphamide should be used with caution with other myelosuppressive
drugs due to potential additive myelosuppression.
• Cyclophosphamide crosses the placenta and is found in milk. It
is potentially both teratogenic and fetogenic. It should not be used during
pregnancy unless the potential benefits outweigh the risks.
• Allopurinol and thiazide diuretics may increase myelosuppression
due to cyclophosphamide.
• Chloramphenicol, imipramine, phenothiazines, potassium iodide and
vitamin A may inhibit cyclophosphamide metabolism.
• Doxorubicin and other cardiotoxic drugs combined with cyclophosphamide
may increase the risk of cardiotoxicity.
• If recognized promptly, oral overdose should be treated aggressively with gut-emptying protocols. The patient should be followed closely and may need hospitalization for additional supportive care.
Dr.
Barbara Forney is a veterinary practitioner in Chester County, Pennsylvania.
She has a master's degree in animal science from the University of Delaware
and graduated from the University of Pennsylvania School of Veterinary Medicine
in 1982.
She began to develop her interest in client education and medical writing 1997. Recent publications include portions of The Pill Book Guide to Medication for Your Dog and Cat, and most recently Understanding Equine Medications published by the Bloodhorse.
Dr. Forney is an FEI veterinarian and an active member of the AAEP, AVMA, and AMWA.
You can purchase books by Dr. Forney at www.exclusivelyequine.com
To help protect veterinary staff and patients from unnecessary exposure to chemotherapy medications and waste, this handling sheet will be included with all chemotherapy prescriptions we dispense.
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risks and benefits of using a particular product. You should consult your doctor
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