Randomized controlled trial of azacitidine in patients with the myelodysplastic syndrome: A study of the cancer and leukemia group B
Randomized controlled trial of azacitidine in patients with the myelodysplastic syndrome: A study of the cancer and leukemia group B
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DOI：
10.1200/jco.2002.04.117
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发表时间：
2002-05-15
影响因子：
45.3
通讯作者：
Holland, JF
中科院分区：
文献类型：
--
作者：
Silverman, LR;Demakos, EP;Holland, JF
目的：高危骨髓增生异常综合征（MDS）患者因骨髓衰竭或转化为急性白血病而具有较高的死亡率。支持治疗是标准疗法。我们先前报道阿扎胞苷（Aza C）对高危MDS患者有效。
患者与方法：对191例MDS患者进行了一项随机对照试验，以比较阿扎胞苷（每28天皮下注射75mg/m²，连续7天）与支持治疗。MDS依据法 - 美 - 英标准定义。采用了新的严格疗效标准。两组均根据需要接受输血和抗生素治疗。支持治疗组中病情恶化的患者可转用阿扎胞苷。
结果：阿扎胞苷组60%的患者有疗效（7%完全缓解，16%部分缓解，37%改善），而接受支持治疗的患者只有5%（改善）（P <.001）。阿扎胞苷组至白血病转化或死亡的中位时间为21个月，支持治疗组为13个月（P =.007）。阿扎胞苷组15%的患者首次事件为转化为急性髓系白血病，而支持治疗组为38%（P =.001）。排除早期转用阿扎胞苷的混杂影响，6个月后的标志性分析显示，阿扎胞苷组的中位生存期额外增加18个月，支持治疗组为11个月（P =.03）。生活质量评估发现，最初随机分配到阿扎胞苷组的患者在身体功能、症状和心理状态方面具有显著的主要优势。
结论：与支持治疗相比，阿扎胞苷治疗可显著提高缓解率、改善生活质量、降低白血病转化风险并提高生存率。对于本研究中所治疗的MDS亚型及特定入选标准的患者，阿扎胞苷提供了一种优于支持治疗的新治疗选择。（C）2002年美国临床肿瘤学会
Purpose: Patients with high-risk myelodysplastic syndrome (MDS) have high mortality from bone marrow failure or transformation to acute leukemia. Supportive care is standard therapy. We previously reported that azacitidine (Aza C) was active in patients with high-risk MDS.Patients and Methods: A randomized controlled trial was undertaken in 191 patients with MDS to compare Aza C (75 mg/m(2)/d subcutaneously for 7 days every 28 days) with supportive care. MDS was defined by French-American-British criteria. New rigorous response criteria were applied. Both arms received transfusions and antibiotics as required. Patients in the supportive care arm whose disease worsened were permitted to cross over to Aza C.Results: Responses occurred in 60% of patients on the Aza C arm (7% complete response, 16% partial response, 37% improved) compared with 5% (improved) receiving supportive care (P < .001). Median time to leukemic transformation or death was 21 months for Aza C versus 13 months for supportive care (P = .007). Transformation to acute myelogenous leukemia occurred as the first event in 15% of patients on the Aza C arm and in 38% receiving supportive care (P = .001). Eliminating the confounding effect of early cross-over to Aza C, a landmark analysis after 6 months showed median survival of an additional 18 months for Aza C and 11 months for supportive care (P = .03). Quality-of-life assessment found significant major advantages in physical function, symptoms, and psychological state for patients initially randomized to Aza C.Conclusion: Aza C treatment results in significantly higher response rates, improved quality of life, reduced risk of leukemic transformation, and improved survival compared with supportive care. Aza C provides a new treatment option that is superior to supportive care for patients with the MDS subtypes and specific entry criteria treated in this study. (C) 2002 by American Society of Clinical Oncology.