Dosage escalation of intravenous cyclophosphamide in cats with cancer

Cyclophosphamide is an alkylating agent used as chemotherapy for cats with lymphoma, carcinomas and sarcomas. Clinical and pharmacokinetic studies of cyclophosphamide in normal and tumor-bearing cats have shown minimal toxicity and cyclophosphamide at clinically used dosages rarely requires dosage adjustment or treatment delays. Dose intensity appears important for treatment of most cancers; the aim of this study was to perform a modified dose escalation study of cyclophosphamide to establish the maximally tolerated dosage (MTD) for intravenous cyclophosphamide in cats. The dose limiting toxicity appeared to be neutropenia, and 30% of cats experienced grade 3 or grade 4 neutropenia at a cyclophosphamide dosage of 480mg/m², which was determined as the MTD. Delayed neutropenia was observed commonly at higher dosages. Thrombocytopenia was less common than neutropenia, and always transient. Gastrointestinal toxicities were uncommon even at MTD. The recommended dosage for single agent cyclophosphamide in cats is 460mg/m² with a post-treatment interval of three weeks, with hematology performed before any subsequent chemotherapy is administered. This dosage appears safe in combination with prednisolone and l-asparaginase; but has not been evaluated in combination with other chemotherapy agents, or with a post-treatment interval shorter than 3 weeks. Such combinations and shorter intervals are found in some protocols, so this recommended cyclophosphamide dose cannot be considered a direct substitute for cyclophosphamide dosages in existing protocols. There is a suggestion that inadequate renal function may exacerbate the myelosuppression of cyclophosphamide which should be further evaluated.