A comparative clinical trial of 5-azacytidine and guanazole in previously treated adults with acute nonlymphocytic leukemia

Abstract

Adults with previously treated acute nonlymphocytic leukemia received either 5-azacytidine or guanazole in a randomized study. Eighteen patients were treated with 5-azacytidine at a dosage of 200–250 mg/m²/day × 5 intravenously (i.v.) and six achieved a remission (five complete). The median duration of complete remission was 100 days. Among the 12 patients who received guanazole, at a dosage of 25–30 g/m²/day × 5 by continuous i.v. infusion, only one partial remission ensued. Patients who responded to 5-azacytidine had a more profound degree of leukopenia (median 600 WBC/mm³) than nonresponders (median 1700 WBC/mm³). Both the time taken to reach the nadir white blood count (median, 14 days) and the duration of the nadir (median, 17 days) were long after each course of 5-azacytidine, particularly for those patients who achieved a remission. Principal toxicities seen after 5-azacytidine administration were gastrointestinal intolerance, fever, and neuromuscular toxicity. Fever was the principal toxicity observed after guanazole therapy; one patient developed erythema nodosum with arthralgias and another, recurrent pulmonary infiltrates. Survival from the start of therapy was clearly longer for the patients receiving 5-azacytidine (median 140 days) because of the prolongation of survival seen in the responding patients (median 266+ days). 5-Azacytidine has significant activity as an induction agent in adults with acute nonlymphocytic leukemia, but guanazole does not appear to be of particular value for patients with this disease.