Phase I-II evaluation of cyclocytidine.

A phase I-II study of cyclocytidine was conducted in 102 patients, 96 of whom had metastatic solid tumors and six of whom had acute leukemia. The drug was administered in 5- or 10-day courses of single daily iv or sc injections of 100-675 mg/m2 day. Two complete and six partial responses were observed in 64 solid tumor patients evaluable for response, 52 of whom had malignant melanoma or adenocarcinoma of gastrointestinal origin. The median duration of the responses was 6 months. An additional seven patients achieved stabilization of their disease for greater than or equal to 2 months. No responses occurred in six patients with acute leukemia. Side effects included nausea and vomiting, postural hypotension, and parotid pain, occurring in approximatley one third of patients receiving greater than 200 mg/m2/day. No myelosuppression was observed in six patients receiving 5-day courses of 100-200 mg/m2/day. Myelosuppressive toxicity became increasingly severe with doses greater than 200 mg/m2/day x 10, related at least in part to prior chemotherapy exposure including the nitrosoureas.