The University of Texas, M.D. Anderson Cancer Center, Department of Leukemia, Houston, TX 77030, USA.
Expert Opin Drug Metab Toxicol. 2011 May;7(5):661-72. doi: 10.1517/17425255.2011.575062.
Acute myeloid leukemia (AML) is a life-threatening malignancy that primarily afflicts an elderly population. Treatment of elderly patients with intensive chemotherapy is associated with high treatment-related morbidity and mortality. Therefore, less toxic approaches involving low-dose decitabine-based regimens are being explored in this patient population.
This drug evaluation article discusses the rationale for targeting aberrant DNA methylation in hematologic malignancies, in particular the myelodysplastic syndromes (MDS) and AML. The authors review the pharmacokinetic data gained from low-dose decitabine, as well as the clinical progress of decitabine in the treatment of hematologic malignancies. Published manuscripts in English were selected from PubMed using a combination of the following search terms: acute myeloid leukemia, pharmacokinetics, decitabine, 5-aza-2'-deoxycytidine, DNA methylation, DNA methyltransferase, myelodysplastic syndrome and leukemia.
Decitabine has established efficacy in MDS and shown promising activity in AML at low doses. Given decitabine’s favorable toxicity profile and emerging clinical efficacy, decitabine may be a low intensity therapeutic option for elderly patients with AML who are considered unfit for aggressive chemotherapy.
急性髓细胞白血病（AML）是一种危及生命的恶性肿瘤，主要影响老年人群。对老年患者进行强化化疗与较高的治疗相关发病率和死亡率相关。因此，在这一患者群体中，正在探索涉及低剂量地西他滨的毒性较小的方法。
本文讨论了针对血液系统恶性肿瘤中异常 DNA 甲基化的靶向治疗的基本原理，特别是骨髓增生异常综合征（MDS）和 AML。作者回顾了低剂量地西他滨的药代动力学数据，以及地西他滨在血液系统恶性肿瘤治疗中的临床进展。使用以下搜索词的组合从 PubMed 中选择了英文已发表的文献：急性髓细胞白血病、药代动力学、地西他滨、5-氮杂-2'-脱氧胞苷、DNA 甲基化、DNA 甲基转移酶、骨髓增生异常综合征和白血病。
地西他滨在 MDS 中具有明确的疗效，在低剂量下在 AML 中显示出有前途的活性。鉴于地西他滨良好的毒性特征和新兴的临床疗效，地西他滨可能是不适合强化化疗的老年 AML 患者的一种低强度治疗选择。
