Cyclophosphamide for Veterinary Use
by Barbara Forney, VMD
Alkylating agent: anti-neoplastic, immune-suppressant
Dogs and cats
May Be Prescribed by Vets for:
Lymphoma, lymphosarcoma, carcinoma, sarcoma, immune-mediated diseases.
No veterinary products approved.
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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 also is used to treat 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).
Dogs and Cats
Cyclophosphamide is used in both dogs and cats as a part of the multi-drug induction protocol to treat 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 (<15-20%) and compliance is relatively easy. There is a large body of literature and research on treating both canine and feline lymphomas. This disease has proved to be treatable; protocols change and are modified regularly as new information becomes available.
Cyclophosphamide has been used to treat 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 no longer is used with prednisone to treat 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 it to urinate frequently also is recommended.
Cyclopphosphamide Side Effects
- Myelosuppression is the dose-limiting side-effect. Neutropenia occurs five 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.
About the Author
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 in 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
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