Patt Y Z, Hersh E M, Reuben J, Claghorn L, Mavligit G
J Biol Response Mod. 1986 Aug;5(4):313-8.
Azimexon, a synthetic derivative of the 2-cyanaziridines, was given intravenously daily for 5 days to 19 cancer patients in a Phase I trial designed to determine the drug's tolerable dose, toxicity, and effects on immune and nonimmune host defense parameters. No myelosuppression, neurologic, renal, hepatic, or gastrointestinal toxicities could be detected. The only toxic side effect observed after 5 days of intravenous azimexon was a self-limiting dose-dependent hemolysis. Absolute lymphocyte count (ALC) increased from a pretreatment value of 0.96 X 10(3)/microliter to 1.56 X 10(3)/microliter on day 21 (p less than 0.05). This increase was induced primarily by the less hemolytic 200-250 mg/m2 doses of azimexon. Among 12 patients given this lower dosage. ALC increased from an average initial value of 0.90 X 10(3)/microliter to 1.86 X 10(3)/microliter on day 21 (p less than 0.01). Absolute number of OKT3+ cells increased from 0.524 to 0.914 X 10(3)/microliter (p less than 0.05) with lower drug doses. The mean absolute number of OKT4+ cells increased from 0.294 on day 0 to 0.574 X 10(3)/microliter on day 21 (p less than 0.05), and the number of OKT8+ cells increased from 0.202 to 0.388 X 10(3)/microliter, with no significant changes in helper/suppressor ratio. Significant increases in mitogenic responses to phytohemagglutinin (PHA) [from 13.4 to 35.7 X 10(3) net cpm (p less than 0.05)] and to concanavalin A (con A) [from 6.4 to 25.6 X 10(3) net cpm (p less than 0.05)] were also observed with higher drug doses. Azimexon may have a role in managing cancer-associated dysregulation of the immune response.
氮咪克松是2-氰基氮丙啶的一种合成衍生物，在一项I期试验中，对19名癌症患者每日静脉给药，持续5天，该试验旨在确定药物的耐受剂量、毒性以及对免疫和非免疫宿主防御参数的影响。未检测到骨髓抑制、神经、肾脏、肝脏或胃肠道毒性。静脉注射氮咪克松5天后观察到的唯一毒性副作用是一种自限性的剂量依赖性溶血。绝对淋巴细胞计数（ALC）从预处理值0.96×10³/微升增加到第21天的1.56×10³/微升（p<0.05）。这种增加主要是由溶血作用较小的200 - 250mg/m²剂量的氮咪克松引起的。在接受较低剂量的12名患者中，ALC从平均初始值0.90×10³/微升增加到第21天的1.86×10³/微升（p<0.01）。较低药物剂量时，OKT3⁺细胞的绝对数量从0.524增加到0.914×10³/微升（p<0.05）。OKT4⁺细胞的平均绝对数量从第0天的0.294增加到第21天的0.574×10³/微升（p<0.05），OKT8⁺细胞数量从0.202增加到0.388×10³/微升，辅助/抑制比例无显著变化。较高药物剂量时，对植物血凝素（PHA）[从13.4增加到35.7×10³净cpm（p<0.05）]和刀豆球蛋白A（Con A）[从6.4增加到25.6×10³净cpm（p<0.05）]的促有丝分裂反应也有显著增加。氮咪克松可能在控制癌症相关的免疫反应失调中发挥作用。
