A randomized trial of liposomal daunorubicin and cytarabine versus liposomal daunorubicin and topotecan with or without thalidomide as initial therapy for patients with poor prognosis acute myelogenous leukemia or myelodysplastic syndrome
A randomized trial of liposomal daunorubicin and cytarabine versus liposomal daunorubicin and topotecan with or without thalidomide as initial therapy for patients with poor prognosis acute myelogenous leukemia or myelodysplastic syndrome
复制标题
DOI：
10.1002/cncr.11180
复制
发表时间：
2003-03-01
期刊：
影响因子：
6.2
通讯作者：
Estey, E
中科院分区：
文献类型：
--
作者：
Cortes, J;Kantarjian, H;Estey, E
背景。由于血管生成可能在急性髓性白血病（AML）和高危骨髓增生异常综合征（MDS）的发病机制中发挥作用，而沙利度胺（Th）已显示出显著的抗血管生成活性，因此本研究旨在探讨Th在治疗AML和MDS患者中的潜在作用以及不含ara- c的方案的可能作用。非inv (16), t(8;21)， -Y或-X细胞遗传学异常的AML或高危MDS成人随机接受柔红霉素（DNX）和ara-C （DA）脂质体或DNX和拓扑替康（DT）。在每组中，患者随机接受单独化疗（DA或DT）或沙利度胺（th或dth）。治疗前后测定血浆血管内皮生长因子（VEGF）水平和微血管密度。84例患者（中位年龄65岁，范围27-84岁）接受治疗。11例接受DT或dth治疗的患者均无应答，这些臂均闭合。37例接受DA治疗的患者中有17例，36例接受DATh治疗的患者中有15例实现了早期完全缓解。中位完全缓解持续时间分别为38周和34周（P = 0.57），中位生存期分别为35周和28周（P = 0.15）。预处理VEGF水平高的患者生存率较低。接受沙利度胺治疗的患者与未接受沙利度胺治疗的患者治疗后VEGF水平或微血管密度的变化无显著差异。作者得出结论，沙利度胺联合化疗对AML或高危MDS患者没有临床获益。(C) 2003年美国癌症协会。
BACKGROUND. Because angiogenesis may play a role in the pathogenesis of acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (MDS), and thalidomide (Th) has shown significant anti-angiogenic activity, this study was designed to investigate the potential role of Th in the treatment of patients with AML and MDS and the possible role of a non-ara-C-containing regimen.METHODS. Adults with AML or high-risk MDS and cytogenetic abnormalities other than inv (16), t(8;21), -Y or -X were randomized to receive liposomal daunorubicin (DNX) and ara-C (DA) or DNX and topotecan (DT). Within each arm, patients were randomized to receive chemotherapy alone (DA or DT) or with thalidomide (DATh or DTTh). Vascular endothelial growth factor (VEGF) plasma levels and microvascular density was measured before and after therapy. Eighty-four patients (median age, 65 years; range, 27-84 years) were treated.RESULTS. None of 11 patients treated with DT or DTTh responded and these arms were closed. Seventeen of 37 patients treated with DA and 15 of 36 treated with DATh achieved an early complete remission. Median complete response duration was 38 and 34 weeks (P = 0.57) and median survival 35 and 28 weeks (P = 0.15), respectively. Patients with high pretreatment VEGF levels had an inferior survival. There was no significant difference in the changes in VEGF levels or microvascular density after treatment in patients who did versus those who did not receive thalidomide.CONCLUSIONS. The authors concluded that thalidomide in combination with chemotherapy does not result in clinical benefit in patients with AML or high-risk MDS. (C) 2003 American Cancer Society.