UF Ematologia, AOU Careggi, via delle Oblate 1, University of Florence, Florence, Italy.
Expert Rev Hematol. 2009 Apr;2(2):121-7. doi: 10.1586/ehm.09.6.
5´-azacitidine is a ring analog of cytosine, differing from the natural nucleoside because it has a nitrogen in lieu of carbon in position five of the pyrimidine. Despite being synthesized approximately 40 years ago it has only recently been employed with success at low doses in the treatment of myelodysplastic syndromes (MDS). This drug has hypomethylating activity and, possibly, exerts its action by reinducing expression of genes silenced by the hypermethylation of CpG islands in their promoters. Azacitidine is administered prevalently subcutaneously (75 mg/m(2)/day for 7 days every 28 days) as the pharmacokinetics and pharmacoavailability are almost equivalent to the intravenous route. It was the first agent demonstrated to delay acute myeloblastic leukemia transformation and to prolong survival for patients with higher risk MDS, and it was approved in 2004 by the US FDA for treatment of all MDS risk categories. Azacitidine allows transfusion independence in more than 40% of treated MDS patients, and has opened a new era in the treatment of MDS and the use of 'epigenetic drugs'. To correctly use this agent and obtain hematological improvements that lead to a prolonged overall survival of MDS patients, hematologists have to modify their perspective and their usual expectations from a chemotherapy-like regimen. Azacitidine may also be administered quite safely to elderly patients presenting comorbidities and it is well tolerated in an out-patient regimen. Its mode of action does not necessarily require cytotoxicity and does not induce a rapid response. Several rounds of therapy and of consequent hypomethylation of target genes are necessary to re-express silenced genes critical to differentiation and the majority of patients will respond after three to six cycles of therapy.
5´-阿扎胞苷是胞嘧啶的环类似物，与天然核苷不同，因为它在嘧啶的 5 位有一个氮而不是碳。尽管它大约在 40 年前被合成，但直到最近才在低剂量下成功用于治疗骨髓增生异常综合征 (MDS)。这种药物具有低甲基化活性，并且可能通过重新诱导启动子中 CpG 岛过度甲基化沉默的基因表达来发挥作用。阿扎胞苷主要通过皮下给药（75mg/m2/天，每 28 天连用 7 天），因为其药代动力学和药效几乎与静脉途径相同。它是第一个被证明可以延迟急性髓细胞白血病转化并延长高危 MDS 患者生存时间的药物，并于 2004 年被美国 FDA 批准用于治疗所有 MDS 风险类别。阿扎胞苷可使超过 40%的 MDS 患者摆脱输血依赖，并在 MDS 的治疗和“表观遗传药物”的应用方面开创了一个新时代。为了正确使用这种药物并获得导致 MDS 患者总生存时间延长的血液学改善，血液科医生必须改变他们对化疗样方案的看法和通常的期望。阿扎胞苷也可以相当安全地用于患有合并症的老年患者，并且在门诊方案中耐受良好。其作用模式不一定需要细胞毒性，也不会引起快速反应。需要几个疗程的治疗和随之而来的靶基因低甲基化，才能重新表达对分化至关重要的沉默基因，大多数患者在治疗三到六个周期后会有反应。
