Continuous infusions of arabinosyl cytosine in patients with neoplastic disease

A study was undertaken of the effects of continuous infusion of arabinosyl cytosine in a group of patients with advanced cancer. Initially all patients received the drug for 7 days. The dose was increased in successive patients. Megaloblastosis occurred with doses as low as 3 mg. per square meter per day for 7 days, although no other hematopoietic effects of consequence occurred at doses less than 30 mg. per square meter per day. Depressions of leukocytes and platelets after 7 days of 30 mg. per square meter of arabinosyl cytosine were comparable to those reported by Talley after a much greater total dose. Compression of the total dose of 210 mg. per square meter into 3 1 2 instead of 7 days resulted in hematopoietic depression equivalent in degree and timing to that noted after the 7 day course. Further decrease of the length of the infusion of 210 mg. per square meter to 1.75, 0.875, or 0.44 days significantly decreased the hematopoietic depressant effects although megaloblastosis was again seen in all. Gastrointestinal toxicity was minor with one week infusions but occurred more frequently when the same total dose was given over a shorter period of time. No therapeutic activity was seen during this study.