氯法拉滨联合阿糖胞苷对比阿糖胞苷单药治疗复发或难治性急性髓系白血病老年患者的疗效：CLASSIC I 试验研究结果。
Clofarabine plus cytarabine compared with cytarabine alone in older patients with relapsed or refractory acute myelogenous leukemia: results from the CLASSIC I Trial.
机构信息
The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
出版信息
J Clin Oncol. 2012 Jul 10;30(20):2492-9. doi: 10.1200/JCO.2011.37.9743. Epub 2012 May 14.
PURPOSE
To compare the receipt of clofarabine plus cytarabine (Clo+Ara-C arm) with cytarabine (Ara-C arm) in patients ≥ 55 years old with refractory or relapsed acute myelogenous leukemia (AML).
PATIENTS AND METHODS
Patients were randomly assigned to receive either clofarabine (Clo) 40 mg/m(2) or a placebo followed by Ara-C 1 g/m(2) for five consecutive days. The primary end point was overall survival (OS). Secondary end points included event-free survival (EFS), 4-month EFS, overall remission rate (ORR; complete remission [CR] plus CR with incomplete peripheral blood count recovery), disease-free survival (DFS), duration of remission (DOR), and safety.
RESULTS
Among 320 patients with confirmed AML (median age, 67 years), the median OS was 6.6 months in the Clo+Ara-C arm and 6.3 months in the Ara-C arm (hazard ratio [HR], 1.00; 95% CI, 0.78 to 1.28; P = 1.00). The ORR was 46.9% in the Clo+Ara-C arm (35.2% CR) versus 22.9% in the Ara-C arm (17.8% CR; P < .01). EFS (HR: 0.63; 95% CI, 0.49 to 0.80; P < .01) and 4-month EFS (37.7% v 16.6%; P < .01) favored the Clo+Ara-C arm compared with Ara-C arm, respectively. DFS and DOR were similar in both arms. Overall 30-day mortality was 16% and 5% for CLO+Ara-C and Ara-C arms, respectively. In the Clo+Ara-C and Ara-C arms, the most common grade 3 to 4 toxicities were febrile neutropenia (47% v 35%, respectively), hypokalemia (18% v 11%, respectively), thrombocytopenia (16% v 17%, respectively), pneumonia (14% v 10%, respectively), anemia (13% v 0%, respectively), neutropenia (11% v 9%, respectively), increased AST (11% v 2%, respectively), and increased ALT (10% v 3%, respectively).
CONCLUSION
Although the primary end point of OS did not differ between arms, Clo+Ara-C significantly improved response rates and EFS. Study follow-up continues, and the role of clofarabine in the treatment of adult patients with AML continues to be investigated.
目的
比较 55 岁及以上复发或难治性急性髓系白血病（AML）患者接受克拉屈滨联合阿糖胞苷（Clo+Ara-C 组）与阿糖胞苷（Ara-C 组）治疗的效果。
方法
患者随机分配接受克拉屈滨（Clo）40mg/m²或安慰剂，随后接受阿糖胞苷 1g/m²，连续 5 天。主要终点是总生存期（OS）。次要终点包括无事件生存期（EFS）、4 个月 EFS、总缓解率（ORR；完全缓解[CR]加不完全外周血细胞计数恢复的 CR）、无病生存期（DFS）、缓解持续时间（DOR）和安全性。
结果
在 320 例确诊为 AML 的患者中（中位年龄 67 岁），Clo+Ara-C 组的中位 OS 为 6.6 个月，Ara-C 组为 6.3 个月（风险比[HR]，1.00；95%CI，0.78 至 1.28；P=1.00）。Clo+Ara-C 组的 ORR 为 46.9%（35.2%CR），而 Ara-C 组为 22.9%（17.8%CR；P<.01）。EFS（HR：0.63；95%CI，0.49 至 0.80；P<.01）和 4 个月 EFS（37.7%比 16.6%；P<.01）分别优于 Ara-C 组。DFS 和 DOR 在两组间相似。两组 30 天总死亡率分别为 16%和 5%。Clo+Ara-C 组和 Ara-C 组最常见的 3-4 级毒性分别为发热性中性粒细胞减少症（47%比 35%）、低钾血症（18%比 11%）、血小板减少症（16%比 17%）、肺炎（14%比 10%）、贫血（13%比 0%）、中性粒细胞减少症（11%比 9%）、AST 升高（11%比 2%）和 ALT 升高（10%比 3%）。
结论
尽管 OS 主要终点在两组间无差异，但 Clo+Ara-C 显著改善了缓解率和 EFS。研究随访仍在继续，克拉屈滨在治疗成人 AML 患者中的作用仍在研究中。
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