Shallis Rory M, Zeidan Amer M
1Department of Internal Medicine, School of Medicine, Yale University, New Haven, CT USA.
3Section of Hematology, Department of Internal Medicine, Yale University, 333 Cedar Street, PO Box 208028, New Haven, CT 06520-8028 USA.
BMC Hematol. 2018 Feb 1;18:4. doi: 10.1186/s12878-018-0095-2. eCollection 2018.
Myelodysplastic syndromes (MDS) encompass a diverse group of hematologic disorders characterized by ineffective and malignant hematopoiesis, peripheral cytopenias and significantly increased risk of progression to acute myeloid leukemia (AML). The hypomethylating agents (HMA) azacitidine and decitabine induce meaningful clinical responses in a significant subset of patients with MDS. Though never compared directly with decitabine, only azacitidine has improved overall survival (OS) compared to conventional care in a randomized trial in patients with higher-risk MDS. The azacitidine regimen used in this pivotal trial AZA-001 included administration at 75 mg/m/day for 7 consecutive days in 28-day cycles (7-0 regimen). Given the logistical difficulties of weekend administration in the 7-0 regimen, as well as in efforts to improve response rates, alternative dosing schedules have been used. In a typical 28-day cycle, administration schedules of 3, 5, 10, and (with the oral version of azacitidine) 14 and 21 days have been used in clinical trials. Most trials that evaluated alternative administration schedules of azacitidine did so in lower-risk MDS and did not directly compare to the 7-0 schedule. Given the lack of randomized prospective studies comparing the 7-0 schedule to the other regimens of azacitidine in MDS, Shapiro et al. conducted a systematic review in an attempt to answer this question. Here we place the findings of this important work in clinical context and review the current knowledge and unresolved issues regarding the impact of administration schedules of azacitidine on outcomes of patients with both lower-risk and higher-risk MDS.
骨髓增生异常综合征（MDS）是一组异质性血液系统疾病，其特征为无效造血和恶性造血、外周血细胞减少以及进展为急性髓系白血病（AML）的风险显著增加。低甲基化药物（HMA）阿扎胞苷和地西他滨在相当一部分MDS患者中可诱导有意义的临床反应。虽然从未将阿扎胞苷与地西他滨直接比较，但在一项针对高危MDS患者的随机试验中，只有阿扎胞苷与传统治疗相比改善了总生存期（OS）。在这项关键试验AZA - 001中使用的阿扎胞苷方案包括以75mg/m²/天的剂量连续给药7天，每28天为一个周期（7 - 0方案）。鉴于7 - 0方案在周末给药存在后勤困难，以及为了提高缓解率，已采用了替代给药方案。在一个典型的28天周期中，临床试验中使用了3、5、10天的给药方案，以及（对于口服阿扎胞苷）14天和21天的给药方案。大多数评估阿扎胞苷替代给药方案的试验是在低危MDS患者中进行的，且未与7 - 0方案直接比较。鉴于缺乏将7 - 0方案与MDS中阿扎胞苷的其他方案进行比较的随机前瞻性研究，Shapiro等人进行了一项系统评价，试图回答这个问题。在此，我们将这项重要工作的结果置于临床背景中，并回顾关于阿扎胞苷给药方案对低危和高危MDS患者结局影响的当前知识和未解决问题。
