Phase I clinical evaluation of 2,3-dihydro-1H-imidazo[1,2-b]pyrazole.
2,3-Dihydro-1H-imidazo[1,2-b]pyrazole, a DNA synthesis inhibitor, was given to 25 patients in a phase I study. The drug was administered by rapid iv infusion daily x 5 days at 3-week intervals at doses ranging from 150 to 1500 mg/m2/day. Side effects were observed with doses of greater than or equal to 1000 mg/m2/day and included nausea and vomiting, diarrhea, dark urine, and anemia. At doses of 1500 mg/m2, three patients had evidence of hemolysis (two had hemoglobinuria and one had acute intravascular hemolysis). The hemolysis was severe enough to cause death in one patient and necessitated abandoning further dose escalation. There was minimal or no myelosuppression at any dose level. No objective tumor regression was observed in any of the 16 patients evaluable for response. Further studies are recommended to carefully evaluate the etiology of the hemolysis before proceeding to a phase II trial. It is unlikely that this drug will prove to be useful unless methods for circumventing hemolysis are developed.
D000328:Adult; D000368:Aged; D000743:Anemia, Hemolytic / Q000139:chemically induced; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use* / Q000633:toxicity; D001853:Bone Marrow / Q000187:drug effects; D004341:Drug Evaluation; D005260:Female; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage / Q000627:therapeutic use / Q000633:toxicity; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D011720:Pyrazoles / Q000008:administration & dosage / Q000627:therapeutic use* / Q000633:toxicity
D000970:Antineoplastic Agents; D007093:Imidazoles; D011720:Pyrazoles