Yap B S, Murphy W K, Burgess M A, Valdivieso M, Bodey G P
Cancer Treat Rep. 1979 Nov-Dec;63(11-12):1849-51.
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.
2,3 - 二氢 - 1H - 咪唑并[1,2 - b]吡唑，一种DNA合成抑制剂，在一项I期研究中给予了25名患者。该药物通过快速静脉输注给药，每天一次，共5天，每3周为一个间隔，剂量范围为150至1500毫克/平方米/天。当剂量大于或等于1000毫克/平方米/天时观察到副作用，包括恶心、呕吐、腹泻、尿液变黑和贫血。在1500毫克/平方米的剂量下，三名患者出现溶血迹象（两名患者出现血红蛋白尿，一名患者出现急性血管内溶血）。溶血严重到足以导致一名患者死亡，因此有必要放弃进一步提高剂量。在任何剂量水平下，骨髓抑制都很轻微或没有。在可评估反应的16名患者中，未观察到任何客观的肿瘤消退。建议在进行II期试验之前，进一步研究仔细评估溶血的病因。除非开发出规避溶血的方法，否则这种药物不太可能被证明是有用的。
