Efficacy of azacitidine compared with that of conventional care regimens in the treatment of higher-risk myelodysplastic syndromes: a randomised, open-label, phase III study.
Efficacy of azacitidine compared with that of conventional care regimens in the treatment of higher-risk myelodysplastic syndromes: a randomised, open-label, phase III study.
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与常规护理方案相比，阿扎西丁氨酸的疗效在治疗高风险的髓质发育异常综合征中：一项随机，开放标签的III期研究。
DOI：
10.1016/s1470-2045(09)70003-8
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发表时间：
2009-03
期刊：
影响因子：
51.1
通讯作者：
Silverman, Lewis R.
中科院分区：
文献类型：
--
作者：
Fenaux, Pierre;Mufti, Ghulam J.;Hellstrom-Lindberg, Eva;Santini, Valeria;Finelli, Carlo;Giagounidis, Aristoteles;Schoch, Robert;Gattermann, Norbert;Sanz, Guillermo;List, Alan;Gore, Steven D.;Seymour, John F.;Bennett, John M.;Byrd, John;Backstrom, Jay;Zimmerman, Linda;McKenzie, David;Beach, C. L.;Silverman, Lewis R.
高危骨髓增生异常综合征患者的药物治疗没有生存优势。在这项试验中，我们旨在评估阿扎胞苷与三种最常见的常规护理方案相比对总生存率的影响。在一项国际、多中心、对照、平行组、开放标签的III期临床试验中，高风险骨髓增生异常综合征患者被随机分配到一对一接受阿扎胞苷（75mg /m²/天，每28天7天）或常规治疗（最佳支持治疗、低剂量阿糖胞苷或随机化前研究者选择的强化化疗）。根据法国、美国、英国和国际预后评分系统分类对患者进行分层；随机分组大小为4个。主要终点是总生存期。对所有指定接受治疗的患者进行疗效分析。本研究已在ClinicalTrials.gov注册，编号NCT00071799。在2004年2月13日至2006年8月7日期间，358名患者被随机分配接受阿扎胞苷（n=179）或传统护理方案（n=179）。阿扎胞苷组的4名患者和常规护理组的14名患者没有接受研究药物，但被纳入意向治疗疗效分析。中位随访21.1个月（IQR为15.1 - 26.9）后，阿扎苷组的中位总生存期为24.5个月（9.9 -未达到），而常规护理组的中位总生存期为15.0个月（5.6 - 24.1）（风险比0.58;95% CI 0.43 - 0.77；分层log-rank p= 0.0001）。最后随访时，阿扎胞苷组有82例死亡，而常规治疗组有113例死亡。在2年时，根据Kaplan-Meier估计，阿扎胞苷组50.8% （95% CI 42.1 - 58.8）的患者存活，而传统护理组为26.2% (18.7 - 34.3)（p< 0.0001）。外周细胞减少是所有治疗中最常见的3-4级不良事件。与常规治疗相比，阿扎胞苷治疗可提高高危骨髓增生异常综合征患者的总生存率。
Drug treatments for patients with high-risk myelodysplastic syndromes provide no survival advantage. In this trial, we aimed to assess the effect of azacitidine on overall survival compared with the three commonest conventional care regimens. In a phase III, international, multicentre, controlled, parallel-group, open-label trial, patients with higher-risk myelodysplastic syndromes were randomly assigned one-to-one to receive azacitidine (75 mg/m² per day for 7 days every 28 days) or conventional care (best supportive care, low-dose cytarabine, or intensive chemotherapy as selected by investigators before randomisation). Patients were stratified by French–American–British and international prognostic scoring system classifications; randomisation was done with a block size of four. The primary endpoint was overall survival. Efficacy analyses were by intention to treat for all patients assigned to receive treatment. This study is registered with ClinicalTrials.gov, number NCT00071799. Between Feb 13, 2004, and Aug 7, 2006, 358 patients were randomly assigned to receive azacitidine (n=179) or conventional care regimens (n=179). Four patients in the azacitidine and 14 in the conventional care groups received no study drugs but were included in the intention-to-treat efficacy analysis. After a median follow-up of 21·1 months (IQR 15·1–26·9), median overall survival was 24·5 months (9·9–not reached) for the azacitidine group versus 15·0 months (5·6–24·1) for the conventional care group (hazard ratio 0·58; 95% CI 0·43–0·77; stratified log-rank p=0·0001). At last follow-up, 82 patients in the azacitidine group had died compared with 113 in the conventional care group. At 2 years, on the basis of Kaplan-Meier estimates, 50·8% (95% CI 42·1–58·8) of patients in the azacitidine group were alive compared with 26·2% (18·7–34·3) in the conventional care group (p<0·0001). Peripheral cytopenias were the most common grade 3–4 adverse events for all treatments. Treatment with azacitidine increases overall survival in patients with higher-risk myelodysplastic syndromes relative to conventional care.