Adis, Auckland, New Zealand.
Drugs. 2012 May 28;72(8):1111-36. doi: 10.2165/11209430-000000000-00000.
Azacitidine (Vidaza®) is a pyrimidine nucleoside analogue of cytidine. This article reviews the clinical efficacy and tolerability of azacitidine in the treatment of patients with myelodysplastic syndromes (MDS)/acute myeloid leukaemia (AML), as well as summarizing its pharmacological properties. The randomized, multicentre Cancer and Leukemia Group B 9221 trial compared the efficacy of subcutaneous azacitidine with that of supportive care alone in patients with MDS fulfilling French-American-British (FAB) classification criteria. The overall response rate, the complete response rate and the complete plus partial response rate were significantly higher in patients receiving azacitidine than in those receiving supportive care alone. The randomized, open-label, multicentre AZA-001 trial compared the efficacy of subcutaneous azacitidine with that of conventional care in adults with higher-risk (i.e. International Prognostic Scoring System intermediate-2-risk or high-risk classification) MDS/AML. Prior to randomization, investigators preselected patients to the conventional care strategy considered most appropriate (i.e. best supportive care, low-dose cytarabine or intensive chemotherapy). The median duration of overall survival was significantly prolonged by 9.4 months in patients with higher-risk MDS receiving azacitidine versus those receiving conventional care. The survival benefit seen with azacitidine versus conventional care was maintained across various patient subgroups (e.g. in patients aged ≥75 years, in those who did not achieve complete remission and in patients with WHO-defined AML). The efficacy of subcutaneous or intravenous azacitidine was also shown in a noncomparative trial in Japanese patients with MDS fulfilling FAB classification criteria, and registry programmes in various countries support the efficacy of azacitidine in patients with MDS. Azacitidine was generally well tolerated in patients with MDS, including in the elderly. Across trials, peripheral cytopenias were the most commonly occurring adverse event in azacitidine recipients, with gastrointestinal adverse events (e.g. nausea, vomiting and diarrhoea) and injection-site reactions among the most commonly occurring non-haematological adverse events. In conclusion, azacitidine is an important agent for use in the treatment of patients with MDS/AML.
阿扎胞苷（Vidaza®）是胞嘧啶的嘧啶核苷类似物。本文综述了阿扎胞苷治疗骨髓增生异常综合征（MDS）/急性髓系白血病（AML）患者的临床疗效和耐受性，并总结了其药理学特性。随机、多中心癌症和白血病组 B9221 试验比较了皮下注射阿扎胞苷与单独支持治疗在符合法国-美国-英国（FAB）分类标准的 MDS 患者中的疗效。接受阿扎胞苷治疗的患者的总反应率、完全反应率和完全加部分反应率明显高于单独接受支持治疗的患者。随机、开放标签、多中心 AZA-001 试验比较了皮下注射阿扎胞苷与传统治疗在高危（即国际预后评分系统中-2 风险或高风险分类）MDS/AML 成人中的疗效。在随机分组之前，研究人员根据最适合的传统治疗策略（即最佳支持治疗、低剂量阿糖胞苷或强化化疗）预选患者。高危 MDS 患者接受阿扎胞苷治疗的总生存期中位数显著延长 9.4 个月，而接受传统治疗的患者则无明显延长。阿扎胞苷与传统治疗相比的生存获益在各种患者亚组中（如年龄≥75 岁的患者、未达到完全缓解的患者和符合世界卫生组织定义的 AML 患者）均得以维持。在符合 FAB 分类标准的日本 MDS 患者的非对照试验和各国的登记计划中也显示了皮下或静脉注射阿扎胞苷的疗效。阿扎胞苷在 MDS 患者中总体耐受性良好，包括在老年患者中。在各项试验中，接受阿扎胞苷治疗的患者最常发生的不良反应是外周血细胞减少，最常发生的非血液学不良反应是胃肠道不良反应（如恶心、呕吐和腹泻）和注射部位反应。总之，阿扎胞苷是治疗 MDS/AML 患者的重要药物。
