Burnett Alan K, Russell Nigel H, Hills Robert K, Kell Jonathan, Cavenagh Jamie, Kjeldsen Lars, McMullin Mary-Frances, Cahalin Paul, Dennis Mike, Friis Lone, Thomas Ian F, Milligan Don, Clark Richard E
Department of Haematology, Cardiff University School of Medicine, Cardiff, United Kingdom;
Department of Haematology, Nottingham University Hospital NHS Trust, Nottingham, United Kingdom;
Blood. 2015 Jun 18;125(25):3878-85. doi: 10.1182/blood-2015-01-623447. Epub 2015 Apr 1.
Modifying induction therapy in acute myeloid leukemia (AML) may improve the remission rate and reduce the risk of relapse, thereby improving survival. Escalation of the daunorubicin dose to 90 mg/m(2) has shown benefit for some patient subgroups when compared with a dose of 45 mg/m(2), and has been recommended as a standard of care. However, 60 mg/m(2) is widely used and has never been directly compared with 90 mg/m(2). As part of the UK National Cancer Research Institute (NCRI) AML17 trial, 1206 adults with untreated AML or high-risk myelodysplastic syndrome, mostly younger than 60 years of age, were randomized to a first-induction course of chemotherapy, which delivered either 90 mg/m(2) or 60 mg/m(2) on days 1, 3, and 5 combined with cytosine arabinoside. All patients then received a second course that included daunorubicin 50 mg/m(2) on days 1, 3, and 5. There was no overall difference in complete remission rate (73% vs 75%; odds ratio, 1.07 [0.83-1.39]; P = .6) or in any recognized subgroup. The 60-day mortality was increased in the 90 mg/m(2) arm (10% vs 5% (hazard ratio [HR] 1.98 [1.30-3.02]; P = .001), which resulted in no difference in overall 2-year survival (59% vs 60%; HR, 1.16 [0.95-1.43]; P = .15). In an exploratory subgroup analysis, there was no subgroup that showed significant benefit, although there was a significant interaction by FLT3 ITD mutation. This trial is registered at http://www.isrctn.com as #ISRCTN55675535.
调整急性髓系白血病（AML）的诱导治疗方案可能会提高缓解率并降低复发风险，从而改善生存率。与45mg/m²的剂量相比，将柔红霉素剂量增至90mg/m²已显示对某些患者亚组有益，并已被推荐为治疗标准。然而，60mg/m²的剂量被广泛使用，且从未与90mg/m²进行过直接比较。作为英国国家癌症研究所（NCRI）AML17试验的一部分，1206例未经治疗的AML或高危骨髓增生异常综合征的成人患者（大多年龄小于60岁）被随机分配接受首个诱导化疗疗程，在第1、3和5天给予90mg/m²或60mg/m²的柔红霉素，并联合阿糖胞苷。所有患者随后接受第二个疗程，在第1、3和5天给予50mg/m²的柔红霉素。完全缓解率（73%对75%；优势比，1.07[0.83 - 1.39]；P = 0.6）或任何公认的亚组中均无总体差异。90mg/m²组的60天死亡率有所增加（10%对5%[风险比（HR）1.98[1.30 - 3.02]；P = 0.001]），这导致总体2年生存率无差异（59%对60%；HR，1.16[0.95 - 1.43]；P = 0.15）。在一项探索性亚组分析中，尽管存在FLT3内部串联重复（ITD）突变的显著交互作用，但没有亚组显示出显著益处。该试验已在http://www.isrctn.com注册，注册号为#ISRCTN55675535。
