Phase I. evaluation of cyclocytidine (NSC-145668)

Cyclocytidine is a repository form of cytosine arabinoside and has a prolonged plasma half-life (8 hours) compared to cytosine arabinoside (12 minutes). A phase I trail was undertaken to establish the maximum tolerated dose. Nineteen patients were entered into the study (ten children, nine adults) and the dose which achieved consistent myelosuppression was established in five escalation increments as 600 mg/m for 10 days. This dose is consistent with previously reported data on the basic pharmacology of cyclocytidine and with optimum dose data in aminal tumor systems. Limiting toxicity, however, was related to the induction of postural hypotension which is not dose related. Recommendation to proceed with phase II studies of cyclocytidine must await clarification of the mechanism and prevention of the postural hypotension.