Von Hoff D D, Slavik M, Muggia F M
Ann Intern Med. 1976 Aug;85(2):237-45. doi: 10.7326/0003-4819-85-2-237.
Clinical studies involving 5-azacytidine, a ring analogue of cytidine, began in Europe in 1967 and the United States in 1970, and we review available preclinical and clinical studies here. The drug possesses cytotoxic, antimicrobial, antineoplastic, abortive, and mutagenic activity in various biological systems. 5-Azacytidine is thought to exert its antineoplastic effect through interference with nucleic acid metabolism. The dose-limiting toxicities are nausea, vomiting, and leukopenia, while the incidence of thrombocytopenia is low. Hepatic toxicity ranges from abnormal findings in liver function tests to hepatic coma. Clinical results in solid tumors are not encouraging, but 5-azacytidine shows consistent antitumor activity in patients with acute myelogenous leukemia resistant to previous treatment. An overall response rate of 36%, with 20% complete remissions, was achieved in 200 previously treated patients with acute myelogenous leukemia. Further studies must define the role of 5-azacytidine alone and in combination for the first-line treatment of acute myelogenous leukemia.
涉及胞苷的环状类似物5-氮杂胞苷的临床研究于1967年在欧洲开始，1970年在美国开始，我们在此回顾现有的临床前和临床研究。该药物在各种生物系统中具有细胞毒性、抗菌、抗肿瘤、堕胎和诱变活性。5-氮杂胞苷被认为通过干扰核酸代谢发挥其抗肿瘤作用。剂量限制性毒性为恶心、呕吐和白细胞减少，而血小板减少的发生率较低。肝毒性范围从肝功能检查异常到肝昏迷。实体瘤的临床结果并不令人鼓舞，但5-氮杂胞苷在对先前治疗耐药的急性髓性白血病患者中显示出一致的抗肿瘤活性。200例先前接受治疗的急性髓性白血病患者的总体缓解率为36%，完全缓解率为20%。进一步的研究必须确定5-氮杂胞苷单独使用和联合使用在急性髓性白血病一线治疗中的作用。
