Dose Schedule and Antitumor Studies of Arabinosyl Cytosine (NSC 63878)^6,7

The effect of dose and schedule of arabinosyl cytosine (ara-C) on bone marrow function and antitumor response was evaluated in 88 patients with metastatic cancer. It was found that: (a) Single doses of ara-C produced no myelosuppressive or antitumor effect. (b) Continuous infusion for 48 or 96 hours resulted in a steep dose-response curve with respect to marrow depression; 18–38% of analyzable patients had tumor regression. (c) Continuous infusion for 24 hours produced an increase in marrow depression with doses up to 1200 mg/sq m, after which further increase in dose did not produce greater myelosuppression. Tumor regression occurred in 10% of these patients. The above dose-marrow response curves, interpreted with a background of experimental data, suggest that a substantial nonproliferating marrow stem cell pool exists in man. (d) Granulocytopenia was more frequent than thrombocytopenia, and lymphopenia did not occur. Platelet “rebound” to greater than 1,000,000 per cu mm following myelosuppression was common. The cell kinetic and therapeutic implications of these observations are discussed.