Homoharringtonine-based induction regimens for patients with de-novo acute myeloid leukaemia: a multicentre, open-label, randomised, controlled phase 3 trial
Homoharringtonine-based induction regimens for patients with de-novo acute myeloid leukaemia: a multicentre, open-label, randomised, controlled phase 3 trial
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基于高三尖杉酯碱的新发急性髓系白血病患者诱导方案：一项多中心、开放标签、随机、对照 3 期试验。
DOI：
10.1016/s1470-2045(13)70152-9
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发表时间：
2013-06-01
期刊：
影响因子：
51.1
通讯作者：
Chen, Sai-Juan
中科院分区：
文献类型：
--
作者：
Jin, Jie;Wang, Jian-Xiang;Chen, Sai-Juan
高三尖杉酯碱为基础的诱导方案在中国已被广泛应用于急性髓系白血病患者。然而，它们的疗效尚未在大规模人群中进行多中心随机对照试验。我们评估了基于高三尖杉酯碱的诱导治疗治疗新诊断的急性髓性白血病的有效性和安全性。方法这项开放标签、随机、对照、III期研究于2007年9月至2011年7月在中国17家机构进行。年龄在14 - 59岁之间的急性髓性白血病未治疗患者被随机分配（通过计算机生成的分配计划，不分层）以1：1：1的比例接受三种诱导方案之一：第1 - 7天高三尖杉酯碱2 mg/m2/天，第1 - 7天阿糖胞苷100 mg/m2/天，第1 - 7天阿拉鲁肽20 mg/天（HAA）;高三尖杉酯碱2 mg/m2/天，第1 - 7天，阿糖胞苷100 mg/m2/天，第1 - 3天柔红霉素40 mg/m2/天（HAD）;或柔红霉素40 - 45 mg/m2/天，第1 - 3天，阿糖胞苷100 mg/m2/天，第1 - 7天（DA）。完全缓解的患者接受两个周期的中等剂量阿糖胞苷治疗（2 g/m2，每12 h一次，第1 - 3天）。主要终点是意向治疗人群中两个周期诱导治疗后达到完全缓解的患者比例和无事件生存期。该试验已在中国临床试验注册中心注册，注册号为ChiCTR-TRC-06000054。结果我们招募了620例患者，其中609例纳入意向治疗分析。HAA组206例患者中有150例（73%）达到完全缓解，DA组205例患者中有125例（61%）达到完全缓解（p = 0.0108）; 3年无事件生存率分别为35.4%（95%CI 28.6 - 42.2）和23.1%（95%CI 17.4 - 29.3; p = 0.0023）。HAD组198例患者中有133例（67%）完全缓解（vs DA，p = 0.20），3年无事件生存率为32.7%（95% CI 26.1 - 39.5; vs DA，p = 0.08）。所有组的不良事件大致相同，除了HAA组的患者更多，（12/206 [5.8%]）和民政事务总署（13/198 [6.6%]）组比DA组在30天内死亡（2/205 [1%]; p = 0.0067 vs HAA; p = 0.0030 vs HAD）。解释高三尖杉酯碱、阿糖胞苷和阿糖胞苷的方案是年轻，新诊断的急性髓性白血病患者。
Background Homoharringtonine-based induction regimens have been widely used in China for patients with acute myeloid leukaemia. However, their efficacy has not been tested in a multicentre randomised controlled trial in a large population. We assessed the efficacy and safety of homoharringtonine-based induction treatment for management of newly diagnosed acute myeloid leukaemia.Methods This open-label, randomised, controlled, phase 3 study was done in 17 institutions in China between September, 2007, and July, 2011. Untreated patients aged 14-59 years with acute myeloid leukaemia were randomly assigned (by a computer-generated allocation schedule without stratification) to receive one of three induction regimens in a 1:1:1 ratio: homoharringtonine 2 mg/m(2) per day on days 1-7, cytarabine 100 mg/m(2) per day on days 1-7, and aclarubicin 20 mg/day on days 1-7 (HAA); homoharringtonine 2 mg/m(2) per day on days 1-7, cytarabine 100 mg/m(2) per day on days 1-7, and daunorubicin 40 mg/m(2) per day on days 1-3 (HAD); or daunorubicin 40-45 mg/m(2) per day on days 1-3 and cytarabine 100 mg/m(2) per day on days 1-7 (DA). Patients in complete remission were offered two cycles of intermediate-dose cytarabine (2 g/m(2) every 12 h on days 1-3). The primary endpoints were the proportion of patients who achieved complete remission after two cycles of induction treatment and event-free survival in the intention-to-treat population. The trial is registered in the Chinese Clinical Trial Register, number ChiCTR-TRC-06000054.Findings We enrolled 620 patients, of whom 609 were included in the intention-to-treat analysis. 150 of 206 patients (73%) in the HAA group achieved complete remission versus 125 of 205 (61%) in the DA group (p=0.0108); 3-year event-free survival was 35.4% (95% CI 28.6-42.2) versus 23.1% (95% CI 17.4-29.3; p=0.0023). 133 of 198 patients (67%) in the HAD group had complete remission (vs DA, p=0.20) and 3-year event-free survival was 32.7% (95% CI 26.1-39.5; vs DA, p=0.08). Adverse events were much the same in all groups, except that more patients in the HAA (12 of 206 [5.8%]) and HAD (13 of 198 [6.6%]) groups died within 30 days than in the DA group (two of 205 [1%]; p=0.0067 vs HAA; p=0.0030 vs HAD).Interpretation A regimen of homoharringtonine, cytarabine, and aclarubicin is a treatment option for young, newly diagnosed patients with acute myeloid leukaemia.