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Reducing the side effects of cyclophosphamide chemotherapy in dogs
  1. Jane Dobson, MA, DVetMed, DipECVIM, MRCVS
  1. Department of Veterinary Medicine, University of Cambridge, Madingley Road, Cambridge CB3 0ES, UK
  1. e-mail: jmd1000{at}

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CYCLOPHOSPHAMIDE is an alkylating agent that acts by cross-linking strands of DNA, thus preventing DNA replication and cell division. Although not licensed for use in dogs, it is frequently used off-licence as a chemotherapeutic agent in the management of lymphoproliferative disorders (lymphoma and leukaemia) as well as some solid tumours (feline mammary carcinoma, thyroid carcinoma, haemangiosarcoma), usually in combination with other cytotoxic drugs. Cyclophosphamide may also be used for its immunosuppressive actions in the treatment of various immune-mediated conditions. Hence, cyclophosphamide is probably the most widely used chemotherapeutic drug in veterinary medicine.

Cyclophosphamide is a pro-drug that is metabolised to active alkylating agents, principally by hepatic microsomal enzymes. There are two main metabolites: 4-hydroxy-cyclophosphamide and acrolein; the former is believed to be mainly responsible for anti-tumour activity and the latter for bladder toxicity. The serum half-life of cyclophosphamide is variable in dogs and the parent drug and metabolites are excreted in the urine, predominantly within the first 24 hours of treatment.

As with many chemotherapeutic agents, cyclophosphamide may cause myelosuppression and gastrointestinal toxicity in some patients, but an unusual adverse effect of cyclophosphamide is sterile haemorrhagic cystitis. This is due to the urotoxic effects of the metabolite acrolein, which can cause oedema, ulceration, haemorrhage and necrosis of the urothelium. Haemorrhagic cystitis is a frequently reported complication of cyclophosphamide therapy in people, occurring in between …

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