pyrazofurin and Leukemia

Six patients with refractory acute nonlymphocytic leukemia were treated with pyrazofurin (15 mg/m2) followed by cytarabine (100 mg/m2) every 12 hours for 6--21 days. All patients cleared their peripheral blood of blast cells but no complete remissions were achieved. Excessive toxicity to skin and mucous membranes was observed. In the doses used, this combination is too toxic for further use. Alternate treatment schedules should be explored.

Topics: Acute Disease; Amides; Antibiotics, Antineoplastic; Cytarabine; Drug Administration Schedule; Drug Synergism; Drug Therapy, Combination; Humans; Leukemia; Pyrazoles; Ribonucleosides; Ribose

Twenty adult patients with relapsed acute nonlymphocytic leukemia were given intravenously the combination of pyrazofurin (PF) 7.5-30 mg/m2 x 1 on day 1 plus 5-azacytidine (AZA) 150-250 mg/m2/d in three divided doses for 5 days. Four patients are early deaths secondary to infection or hemorrhage and are invaluable for response. Three patients achieved a response (two patients had a CR, the third patient had a CR, relapsed, and then a PR). Duration of response was short (41-94 days). Hematologic toxicity was universal and similar at al dose ranges studied. The median pretreatment WBC and platelet counts were 500 and 32,000/microliter, respectively, and the nadirs were 500 and 15,000/microliter. Recovery only occurred in those patients who achieved a response. Nonhematologic toxicity consisted of skin rash (100% of the courses), mucositis (60%), myalgia (93%), nausea and vomiting (83%), and hypotension (47%). In conclusion, although there is interesting preclinical data to suggest that the combination of PF and AZA has synergistic cytotoxicity on leukemic cells, this human clinical trial demonstrates that the combination has significantly more nonhematologic toxicity than AZA alone and no therapeutic advantage over treatment with AZA alone.

Topics: Acute Disease; Adolescent; Adult; Aged; Amides; Antibiotics, Antineoplastic; Azacitidine; Drug Evaluation; Female; Humans; Leukemia; Male; Middle Aged; Pyrazoles; Ribonucleosides; Ribose

Topics: Amides; Animals; Antibiotics, Antineoplastic; Azacitidine; Cell Survival; Drug Synergism; Drug Therapy, Combination; Female; Humans; In Vitro Techniques; Leukemia; Leukemia, Experimental; Mice; Mice, Inbred Strains; Orotic Acid; Pyrazoles; Ribonucleosides; Ribose