Peter H H, Dziuba-Traber H, Boerner D
Eur J Cancer Clin Oncol. 1984 Mar;20(3):353-9. doi: 10.1016/0277-5379(84)90081-6.
The 2-cyanaziridin derivative, azimexon (E), has previously been shown to have certain immunomodulatory properties. In particular, the induction of leukocytosis, the stimulation of delayed-type hypersensitivity reactions and the synergistic effect of azimexon and antibiotics in the control of lethal bacterial and fungal infections in mice prompted us to test azimexon as an adjuvant to chemotherapy in 14 myeloma patients. In a randomized double-blind cross-over study 3 X 600 mg of azimexon were added to one of two consecutive, identical chemotherapy courses consisting of melphalan/prednisone (MP) or vincristine/cyclophosphamide/melphalan/prednisone (VCMP). Chemotherapy was given during days 1-4 and azimexon or placebo were added on days 6, 10 and 14. Blood counts and natural killer (NK) cell testing were performed on days 0 and 21 of each course. With the exception of a transient taste irritation in two patients, azimexon caused no subjective side-effects. White blood cell counts were not altered by the drug; red blood cells and hemoglobin showed a borderline depression after azimexon. NK activities measured against three target cell lines (K562, IGR3, L1210) tended to increase after azimexon treatment. When added in vitro to NK assays azimexon caused a slight increase of NK activity at concentrations of 0.01-0.25 mu/ml, whereas concentrations above 1 microgram/ml were inhibitory. The increase of NK activity by azimexon was not due to the induction of interferon in the effector lymphocyte population.
2-氰基氮丙啶衍生物阿齐美克（E）先前已被证明具有一定的免疫调节特性。特别是，阿齐美克能诱导白细胞增多、刺激迟发型超敏反应，并且在控制小鼠致死性细菌和真菌感染方面，它与抗生素具有协同作用，这些促使我们在14例骨髓瘤患者中测试阿齐美克作为化疗佐剂的效果。在一项随机双盲交叉研究中，将3×600毫克阿齐美克添加到由美法仑/泼尼松（MP）或长春新碱/环磷酰胺/美法仑/泼尼松（VCMP）组成的两个连续、相同化疗疗程中的一个疗程中。化疗在第1 - 4天进行，阿齐美克或安慰剂在第6、10和14天添加。在每个疗程的第0天和第21天进行血细胞计数和自然杀伤（NK）细胞检测。除了两名患者出现短暂的味觉不适外，阿齐美克未引起主观副作用。该药物未改变白细胞计数；阿齐美克治疗后红细胞和血红蛋白出现临界性降低。用三种靶细胞系（K562、IGR3、L1210）检测NK活性，阿齐美克治疗后NK活性有升高趋势。当在体外添加到NK检测中时，阿齐美克在浓度为0.01 - 0.25微克/毫升时会使NK活性略有增加，而浓度高于1微克/毫升则具有抑制作用。阿齐美克使NK活性增加并非由于效应淋巴细胞群体中干扰素的诱导。
