The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA.
J Clin Oncol. 2013 Jul 10;31(20):2548-53. doi: 10.1200/JCO.2012.44.6823. Epub 2013 Jun 3.
This open-label, randomized phase II trial assessed efficacy and tolerability of two low-dose regimens of subcutaneous (SC) decitabine in patients with low- or intermediate-1-risk myelodysplastic syndrome (MDS).
Patients received decitabine 20 mg/m(2) SC per day for 3 consecutive days on days 1, 2, and 3 every 28 days (schedule A) or 20 mg/m(2) SC per day once every 7 days on days 1, 8, and 15 every 28 days (schedule B) for up to 1 year. Primary efficacy end point was overall improvement rate (OIR: complete remission [CR], partial remission [PR], marrow CR [mCR], or hematologic improvement [HI]). Secondary end points were HI, transfusion independence, cytogenetic response, overall survival (OS), and time to acute myeloid leukemia or death.
Efficacy and safety populations were identical: schedule A, n = 43; schedule B, n = 22. Median time from MDS diagnosis to treatment was 3.6 months; 89% had de novo MDS. The trial was terminated early on achievement of protocol-defined OIR superiority of schedule A over schedule B; OIR was 23% for schedule A (seven CRs, three HIs) and 23% for schedule B (one mCR, one PR, three HIs). No differences were observed in secondary end points. Median OS was not reached; approximately 70% of patients were alive at 500 days. Patients in schedule A (67%) and schedule B (59%) were RBC/platelet independent on study. The most frequent drug-related adverse events overall were neutropenia (28% v 36%), anemia (23% v 18%), and thrombocytopenia (16% v 32%).
In this phase II study, low-dose decitabine showed promising results in patients with low- or intermediate-1-risk MDS.
本开放标签、随机 2 期临床试验评估了两种低剂量皮下（SC）地西他滨方案治疗低危或中危-1 级骨髓增生异常综合征（MDS）患者的疗效和耐受性。
患者每 28 天接受 3 天的连续地西他滨治疗，方案 A 为 20mg/m2 SC 每天一次，方案 B 为 20mg/m2 SC 每天一次，每 7 天一次，共 1 年。主要疗效终点为总体缓解率（OIR：完全缓解[CR]、部分缓解[PR]、骨髓 CR [mCR]或血液学改善[HI]）。次要终点为 HI、输血独立性、细胞遗传学反应、总生存（OS）和急性髓系白血病或死亡时间。
疗效和安全性人群相同：方案 A，n=43；方案 B，n=22。从 MDS 诊断到治疗的中位时间为 3.6 个月；89%为初发 MDS。该试验因方案 A 优于方案 B 的 OIR 优越性而提前终止；方案 A 的 OIR 为 23%（7 例 CR、3 例 HI），方案 B 的 OIR 为 23%（1 例 mCR、1 例 PR、3 例 HI）。次要终点无差异。中位 OS 未达到；大约 70%的患者在 500 天仍存活。方案 A（67%）和方案 B（59%）的患者在研究期间红细胞/血小板独立。总体而言，最常见的药物相关不良事件是中性粒细胞减少症（28%对 36%）、贫血症（23%对 18%）和血小板减少症（16%对 32%）。
在这项 2 期研究中，低剂量地西他滨在低危或中危-1 级 MDS 患者中显示出有前景的结果。
