Petti M C, Mandelli F, Zagonel V, De Gregoris C, Merola M C, Latagliata R, Gattei V, Fazi P, Monfardini S, Pinto A
Department of Human Biopathology, University La Sapienza, Rome, Italy.
Leukemia. 1993 May;7 Suppl 1:36-41.
5-Aza-2'-deoxycytidine (Decitabine) is a new cytosine analog with potent antileukemic activity and able to induce in vitro gene activation and cellular differentiation by a mechanism probably involving DNA hypomethylation. The aim of this pilot study was to evaluate the efficacy and the toxicity of Decitabine, used as single induction agent, in the treatment of poor prognosis acute myeloid leukemia (AML) patients, and to explore its mechanism of action. A total of 12 patients were treated with Decitabine at 90-120 mg/m2 as a four hour intravenous infusion, three times daily for three consecutive days every four to six weeks. A minimum of two courses were required for response evaluation and to consider a patient as therapeutic failure. A total of 10/12 patients were fully evaluable for response; three patients achieved a complete remission (CR) and one a partial remission (PR). Extra-hematological toxicity was generally mild. As for the mechanism of action, both a differentiation induction effect and a cytotoxic mechanism have been observed. In particular, CRs and PRs were probably obtained through the induction of leukemia cell differentiation as shown by the kinetic of remission and immunotyping studies. The preliminary results of this ongoing study suggest that Decitabine may have a prominent role in the treatment of those AML patients with poor general conditions and/or advanced age.
5-氮杂-2'-脱氧胞苷（地西他滨）是一种新型胞嘧啶类似物，具有强大的抗白血病活性，可能通过涉及DNA低甲基化的机制在体外诱导基因激活和细胞分化。本初步研究的目的是评估地西他滨作为单一诱导剂治疗预后不良的急性髓系白血病（AML）患者的疗效和毒性，并探索其作用机制。共有12例患者接受地西他滨治疗，剂量为90-120mg/m²，静脉滴注4小时，每天3次，连续3天，每4至6周重复一次。至少需要两个疗程进行疗效评估，将患者视为治疗失败。共有10/12例患者可进行充分的疗效评估；3例患者达到完全缓解（CR），1例达到部分缓解（PR）。血液外毒性一般较轻。至于作用机制，观察到了分化诱导效应和细胞毒性机制。特别是，如缓解动力学和免疫分型研究所显示的，CR和PR可能是通过诱导白血病细胞分化获得的。这项正在进行的研究的初步结果表明，地西他滨在治疗那些一般状况较差和/或年龄较大的AML患者中可能具有重要作用。
