The use of liposomal daunorubicin (DaunoXome) in acute myeloid leukemia
The use of liposomal daunorubicin (DaunoXome) in acute myeloid leukemia
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DOI：
10.1080/10428190500052438
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发表时间：
2005-06-01
影响因子：
2.6
通讯作者：
Anagnostopoulos, A
中科院分区：
文献类型：
--
作者：
Fassas, A;Anagnostopoulos, A
改变药物脂质体制剂的药代动力学可以降低毒性并允许高剂量给药。据报道，柔红霉素脂质体制剂（DaunoXome, L-DNR）由于脂质体部分在体内的缓慢分布而产生较高的血浆曲线下平均面积（AUC）水平，也减少了柔红霉素向有毒但无活性的柔红霉素的转化。动物和体外研究表明，肿瘤内和细胞内药物水平增加，导致细胞毒性增强，甚至在多药耐药细胞系中也是如此，而正常组织毒性，包括心脏毒性，可能会降低。L-DNR已被测试作为单一药物或与阿拉伯糖胞嘧啶联合治疗复发的急性髓系白血病（AML）患者、新诊断的AML患者或最初缓解诱导治疗失败的疾病患者。结果表明，L-DNR可在高达150mg /m(2)的高剂量下使用3天，安全且毒性可接受。据报道，其抗白血病活性至少等于或优于游离柔红霉素。粘膜炎比心脏毒性更常见，AML患者首次复发时完全缓解率高。然而，L-DNR在疗效和毒性方面的优势，只有通过前瞻性临床研究将L-DNR与游离柔红霉素或其他方案进行比较才能显示出来。两项比较试验目前正在AML患者中进行，一项针对儿童，另一项针对老年人，分别由国际BFM和GIMEMA组织进行。
Altered pharmacokinetics of liposomal formulations of drugs can diminish toxicity and allow the administration of the encapsulated drug at high doses. The liposomal formulation of daunorubicin (DaunoXome, L-DNR) has been reported to produce high mean area under the plasma curve (AUC) levels due to a slow distribution of the liposomal moiety into the body and also to reduce the conversion of daunorubicin to the toxic, but inactive, daunorubicinol. Animal and in vitro studies have shown increased intratumor and intracellular levels of the drug, resulting in enhanced cytotoxicity, even in multidrug-resistant cell lines, while normal tissue toxicity, including cardiotoxicity, may be reduced. L-DNR has been tested as a single agent or in combination with arabinosyl cytosine in the treatment of patients with acute myeloid leukemia (AML) in relapse or in patients with newly diagnosed AML or with disease failing initial remission-induction therapy. The results have indicated that L-DNR can be used at high doses, up to 150 mg/m(2) for 3 days, safely with acceptable toxicity. The antileukemia activity has been reported to be at least equal or superior to that of free daunorubicin. Mucositis appeared more frequently than cardiotoxicity and high complete remission rates have been reported in patients with AML in first relapse. However, the superiority of L-DNR with regard to efficacy and toxicity will only be shown by prospective clinical studies comparing L-DNR with free daunorubicin or other regimens. Two comparative trials are currently active in AML patients, one in children and another in the elderly, run by the international BFM and GIMEMA groups, respectively.