The impact of dose escalation and resistance modulation in older patients with acute myeloid leukaemia and high risk myelodysplastic syndrome: the results of the LRF AML14 trial
The impact of dose escalation and resistance modulation in older patients with acute myeloid leukaemia and high risk myelodysplastic syndrome: the results of the LRF AML14 trial
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DOI：
10.1111/j.1365-2141.2009.07604.x
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发表时间：
2009-05-01
影响因子：
6.5
通讯作者：
Wheatley, Keith
中科院分区：
文献类型：
--
作者：
Burnett, Alan K.;Milligan, Donald;Wheatley, Keith
急性髓系白血病 (AML)14 试验解决了主要患有 AML 和高危骨髓增生异常综合征的 60 岁以上患者的四个治疗问题：(i) 柔红霉素 50 mg/m(2) 与 35 mg/m(2)； (ii) 在两个 DA 诱导疗程中，阿糖胞苷 200 mg/m(2) 与 400 mg/m(2) 比较； (iii) 在试验的一部分中，分配柔红霉素 35 mg/m(2) 的患者也以 1:1:1 的随机比例随机接受或不接受多药耐药调节剂 PSC-833； (iv) 总共三个或四个疗程。总共招募了 1273 名患者。有效率62%（完全缓解54%，完全缓解无血小板/中性粒细胞恢复8%）； 5 年生存率为 12%。在剂量递增随机化或第四个疗程中均未观察到任何益处。由于诱导死亡，PSC-833 组存在反应较差的趋势。多变量分析确定了细胞遗传学，将白细胞计数、年龄和继发性疾病作为结果的主要预测因素。尽管 Pgp 表达和功能高的患者的反应和生存率较差，但这并不是一个独立的预后因素，并且 PSC-833 并未改变这一因素。总之，这四种干预措施并未改善老年患者的预后。需要探索新的药物并需要新颖的试验设计，以最大限度地提高及时取得进展的前景。
The acute myeloid leukaemia (AML)14 trial addressed four therapeutic questions in patients predominantly aged over 60 years with AML and High Risk Myelodysplastic Syndrome: (i) Daunorubicin 50 mg/m(2) vs. 35 mg/m(2); (ii) Cytarabine 200 mg/m(2) vs. 400 mg/m(2) in two courses of DA induction; (iii) for part of the trial, patients allocated Daunorubicin 35 mg/m(2) were also randomized to receive, or not, the multidrug resistance modulator PSC-833 in a 1:1:1 randomization; and (iv) a total of three versus four courses of treatment. A total of 1273 patients were recruited. The response rate was 62% (complete remission 54%, complete remission without platelet/neutrophil recovery 8%); 5-year survival was 12%. No benefits were observed in either dose escalation randomization, or from a fourth course of treatment. There was a trend for inferior response in the PSC-833 arm due to deaths in induction. Multivariable analysis identified cytogenetics, presenting white blood count, age and secondary disease as the main predictors of outcome. Although patients with high Pgp expression and function had worse response and survival, this was not an independent prognostic factor, and was not modified by PSC-833. In conclusion, these four interventions have not improved outcomes in older patients. New agents need to be explored and novel trial designs are required to maximise prospects of achieving timely progress.