5-AZACYTIDINE (NSC 102816) - NEW DRUG FOR TREATMENT OF MYELOBLASTIC LEUKEMIA

Abstract

The pyrimidine analog, 5-azacytidine (NSC-102816), was administered by continuous i.v. infusion in Ringer''s lactate in increasing doses to sets of patients with metastatic cancer to establish a dose sufficient to produce mild toxicity. Twenty-one patients (23 trials) were treated with doses of 50-200 mg/m2 per day for 5 days every 2-4 wk. Nausea and vomiting were moderate and easily preventable. Doses of 100-200 mg/m2 for 5 days every 14 days produced granulocytopenia, usually after 2 courses. Less toxicity was observed when courses were given every 21-28 days. Forty-five patients with previously treated and refractory acute myeloblastic leukemia were treated. The majority received doses of 150 mg/m2 for 5 days every 2 wk. Eleven (24%) complete remissions and 4 partial remissions were observed. The number of courses to achieve remission averaged 3 and required an average of 59 days. Nine patients with blastic crisis of chronic myeloblastic leukemia and 4 with refractory acute lymphoblastic leukemia failed to respond. 5-Azacytidine administered by continuous infusion is well tolerated and is an active compound in acute myeloblastic leukemia.