Evaluation of toxicity of a chronic alternate day metronomic cyclophosphamide chemotherapy protocol in dogs with naturally occurring cancer.

Sterile hemorrhagic cystitis (SHC) is an important complication of cyclophosphamide chemotherapy in dogs as it is reported in up to 23% of cases with various protocols. The current study reports toxicities of a protocol of metronomic cyclophosphamide, and identifies risk factors for development of adverse effects. A retrospective cohort study of dogs treated with metronomic cyclophosphamide at an intended dose of 25 mg/m2 every other day was conducted. Fifty dogs were included with a median length of treatment of 90 days (range: 1 to 1305 days). Treatment was discontinued in 22 dogs (44%) due to adverse effects; 16 dogs (32%) developed SHC after a median time of 127.5 days (range: 54 to 1305 days). Higher cumulative dose was significantly associated with a higher risk of SHC development (P = 0.048). Therefore, close monitoring and/or prophylactic treatments should be considered for patients receiving chronic metronomic cyclophosphamide therapy.