优化年轻急性髓细胞白血病患者的化疗：英国医学研究理事会 AML15 试验的结果。

Optimization of chemotherapy for younger patients with acute myeloid leukemia: results of the medical research council AML15 trial.

机构信息

Alan K. Burnett and Robert K. Hills, Cardiff University School of Medicine, Cardiff; Nigel H. Russell, Nottingham University Hospital National Health Service Trust, Nottingham; Ann E. Hunter, Leicester Royal Infirmary, Leicester; John Yin, Manchester Royal Infirmary, Manchester Brenda E.S. Gibson, Royal Hospital for Sick Children, Yorkhill, Glasgow; Keith Wheatley, Cancer Research UK Clinical Trials Unit, University of Birmingham; and Donald Milligan, Birmingham Heartlands Hospital, Birmingham, United Kingdom; and Lars Kjeldsen, Rigshopitalet, Copenhagen, Denmark.

出版信息

J Clin Oncol. 2013 Sep 20;31(27):3360-8. doi: 10.1200/JCO.2012.47.4874. Epub 2013 Aug 12.

DOI:10.1200/JCO.2012.47.4874

PMID:23940227

Abstract

PURPOSE

Treatment outcomes in younger patients with acute myeloid leukemia (AML) have improved, but optimization and new combinations are needed. We assess three combinations in induction and consolidation.

PATIENTS AND METHODS

Younger untreated patients with AML (median age, 49 years; range, 0 to 73 years) were randomly allocated to two induction courses of daunorubicin and cytarabine (DA) with or without etoposide (ADE; n = 1983) or ADE versus fludarabine, cytarabine, granulocyte colony-stimulating factor, and idarubicin (FLAG-Ida; n = 1268), and to amsacrine, cytarabine, etoposide, and then mitoxantrone/cytarabine (MACE-MidAC) or high-dose cytarabine (n = 1,445) 3 g/m(2) or 1.5 g/m(2) (n = 657) in consolidation, and finally to a fifth course (cytarabine) or not (n = 227).

RESULTS

Overall remission rates were similar for DA versus ADE (84% v 86%; P = .14) and ADE versus FLAG-Ida (86% v 85%; P = .7), with more course 1 remissions after FLAG-Ida (77%) reducing relapse (38% v 55%; P < .001) and improving relapse-free survival (45% v 34%; P = .01), overall and in subgroups, but with increased myelosuppression, reducing participation in the consolidation randomization. Overall outcomes were similar between MACE/MidAc and high-dose cytarabine (1.5/3.0 g/m(2)), but cytarabine required less supportive care. MACE/MidAc was superior for high-risk patients. A fifth course provided no benefit. The outcome for recipients of only two FLAG-Ida courses were not different from that with DA/ADE with consolidation.

CONCLUSION

FLAG-Ida is an effective remission induction treatment, with a high complete remission rate after course 1 and reduced relapse. Consolidation with MACE/MidAc is similar overall to high-dose cytarabine, but superior in high-risk patients. Cytarabine at 1.5 g/m(2) is equivalent to a 3 g/m(2) dose. A fifth course is unnecessary. In patients receiving FLAG-Ida (two courses) and cytarabine (two courses), 8-year survival was 63% for patients with intermediate-risk and 95% for those with favorable-risk disease.

摘要

目的

年轻急性髓系白血病（AML）患者的治疗结果已得到改善，但仍需优化和新的联合治疗。我们评估了诱导和巩固治疗中的三种联合治疗方案。

方法

对中位年龄为 49 岁（范围为 0 至 73 岁）的未经治疗的年轻 AML 患者进行随机分组，分别接受包含柔红霉素和阿糖胞苷的两个诱导疗程（DA）联合或不联合依托泊苷（ADE；n=1983），或接受 ADE 联合氟达拉滨、阿糖胞苷、粒细胞集落刺激因子和伊达比星（FLAG-Ida；n=1268），或接受三氧化二砷、阿糖胞苷、依托泊苷，然后米托蒽醌/阿糖胞苷（MACE-MidAC）或大剂量阿糖胞苷（3 g/m2或 1.5 g/m2；n=1445）巩固治疗，最后进行第五个疗程（阿糖胞苷）或不进行（n=227）。

结果

DA 与 ADE 相比（84%比 86%；P=0.14），以及 ADE 与 FLAG-Ida 相比（86%比 85%；P=0.7），总体缓解率相似，但 FLAG-Ida 方案（77%）在第 1 个疗程后缓解率更高，降低了复发率（38%比 55%；P<0.001），改善了无复发生存率（45%比 34%；P=0.01），且在所有亚组中均如此，但骨髓抑制更严重，降低了参与巩固治疗随机分组的比例。MACE/MidAC 与高剂量阿糖胞苷（1.5/3.0 g/m2）的总体结果相似，但阿糖胞苷需要的支持性护理更少。高危患者中，MACE/MidAC 更有优势。第五个疗程无获益。仅接受两个 FLAG-Ida 疗程的患者的结果与接受 DA/ADE 联合巩固治疗的患者无差异。

结论

FLAG-Ida 是一种有效的缓解诱导治疗方案，第 1 个疗程后完全缓解率高，复发率低。MACE/MidAC 巩固治疗与大剂量阿糖胞苷总体相似，但在高危患者中更有优势。阿糖胞苷 1.5 g/m2 与 3 g/m2 剂量等效。第五个疗程无必要。接受 FLAG-Ida（两个疗程）和阿糖胞苷（两个疗程）治疗的患者中，中危患者的 8 年生存率为 63%，低危患者的 8 年生存率为 95%。