Evaluation of low-dose metronomic (LDM) cyclophosphamide toxicity in cats with malignant neoplasia

Oral administration of low-dose cyclophosphamide in pets with spontaneously occurring malignant neoplasms has become a common practice in veterinary medicine. The purpose of this retrospective study was to investigate toxicity events in cats with spontaneous malignancies receiving cyclophosphamide as a metronomic therapy for at least 1 month. The number and severity of clinical, haematological and biochemical adverse events were recorded according to the Veterinary Cooperative Oncology Group's Common Terminology Criteria for Adverse Events v1.1 classification scheme. Twenty-four cats were enrolled in the study with a total number of 27 neoplasms: 13 sarcomas, 12 carcinomas, one melanoma and one neuroendocrine tumour. Seventeen cats presented with macroscopic disease, while seven had microscopic disease. Seven cats (29%) had metastasis either to the regional lymph nodes and/or distant sites at the time of study enrolment. Additional medications, administered concurrently, included non-steroidal anti-inflammatory drugs (17), toceranib (4) and thalidomide (7). Four cats showed grade I gastrointestinal toxicity during the first month of treatment, which was controlled with antiemetics. Overall, 2/24 cats (8%) showed grade I haematological toxicities and 1/24 (4%) showed grade I renal toxicity in the first 4 weeks. Median follow-up for all cats was 30 days (range 30-360 days). For the 15 cats with follow-up longer than 1 month the only additional toxicities observed were two grade III and one grade II azotaemia that occurred after 2 months of therapy. Low-dose cyclophosphamide seems to be a well-tolerated option for cats bearing primary or metastatic tumours. Evaluation of toxicity after long-term administration is still needed.