Phase I dose escalating study of oral cyclophosphamide in tumour-bearing cats

Cyclophosphamide is an alkylating agent used to treat cats with lymphoma, carcinomas and sarcomas. However, no clear consensus exists regarding the maximum tolerated dose (MTD) of oral cyclophosphamide in cats. Toxicities are rarely reported at published oral dosages of cyclophosphamide (200-300 mg/m²). The primary aim of this prospective study was to determine the MTD of oral cyclophosphamide in tumour-bearing cats via a modified phase I trial. A secondary aim was to define any toxicity. Forty-six client-owned tumour-bearing cats were enrolled. The cyclophosphamide dosage was escalated by approximately 10% (300, 330, 360, 400, 440, 460 and 480 mg/m²) in cohorts of at least six cats. The MTD of oral cyclophosphamide in this study was 460 mg/m² with an inter-treatment interval of two to three weeks. Haematology is recommended 7 and 14 days after first cyclophosphamide treatment, and immediately before each subsequent dosage of cyclophosphamide or any potentially myelosuppressive chemotherapy agent. The dose-limiting toxicity was neutropenia with nadir at 7-21 days. This higher dosage was considered safe in combination with prednisolone and L-asparaginase. However, the higher dose of oral cyclophosphamide has not been evaluated in combination with other chemotherapy agents and thus should not be administered with these agents.