Infusion of 5-Azacytidine (5-AZA) into the fourth ventricle or resection cavity in children with recurrent posterior Fossa Ependymoma: a pilot clinical trial.
Infusion of 5-Azacytidine (5-AZA) into the fourth ventricle or resection cavity in children with recurrent posterior Fossa Ependymoma: a pilot clinical trial.
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将 5-氮杂胞苷 (5-AZA) 输注到患有复发性后窝室管膜瘤的儿童的第四脑室或切除腔中：一项试点临床试验。
DOI：
10.1007/s11060-018-03055-1
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发表时间：
2019
影响因子：
3.9
通讯作者：
Taylor,MichaelD
中科院分区：
文献类型：
--
作者：
Sandberg,DavidI;Yu,Bangning;Patel,Rajan;Hagan,John;Miesner,Emilie;Sabin,Jennifer;Smith,Sarah;Fletcher,Stephen;Shah,ManishN;Sirianni,RachaelW;Taylor,MichaelD
背景DNA甲基化抑制剂是治疗起源于脑后窝的室管膜瘤的合理候选药物。我们的目的是测试DNA甲基化抑制剂5-氮杂胞苷(5-azacytidine，5-AZA)直接注入第四脑室或肿瘤切除腔内治疗儿童复发性室管膜瘤的安全性。材料与方法对发自后颅窝的复发性室管膜瘤患者，行最大安全的肿瘤次全切除。肿瘤切除结束后，手术将导管置入第四脑室或肿瘤切除腔，并连接脑室通路装置。术后用电影相位对比磁共振成像(MRI)证实脑脊液从后颅窝流向骶骨。计划每周连续12次输注10毫克(Mg)的5-氮胞苷(AZA)。通过MRI扫描和脑脊液细胞学检查监测疾病反应。一名患者因肿瘤切除后的手术并发症在计划中的5-AZA输注前被撤回。其余5名患者分别接受了8、12、12、12和12次输液。没有严重的不良事件或新的神经功能障碍归因于5-AZA注射。接受5-AZA注射的5名室管膜瘤患者均为进展性疾病。然而，5例患者中有2例至少有一处脑室病变缩小。结论5-AZA可以注入第四脑室或后颅窝肿瘤切除腔内，而不会造成神经毒性。未来有必要进行更高剂量和/或更高剂量频率的研究。
BackgroundDNA methylation inhibitors are logical therapeutic candidates for ependymomas originating in the posterior fossa of the brain. Our objective was to test the safety of infusing 5-Azacytidine (5-AZA), a DNA methylation inhibitor, directly into cerebrospinal fluid (CSF) spaces of the fourth ventricle or tumor resection cavity in children with recurrent ependymoma originating in the posterior fossa.Materials and methodsIn patients with recurrent ependymoma whose disease originated in the posterior fossa, a maximal safe subtotal tumor resection was performed. At the conclusion of the tumor resection, a catheter was surgically placed into the fourth ventricle or tumor resection cavity and attached to a ventricular access device. CSF flow from the posterior fossa to the sacrum was confirmed by CINE phase contrast magnetic resonance imaging (MRI) postoperatively. 12 consecutive weekly 10 milligram (mg) infusions of 5-Azacytidine (AZA) were planned. Disease response was monitored with MRI scans and CSF cytology.ResultsSix patients were enrolled. One patient was withdrawn prior to planned 5-AZA infusions due to surgical complications after tumor resection. The remaining five patients received 8, 12, 12, 12, and 12 infusions, respectively. There were no serious adverse events or new neurological deficits attributed to 5-AZA infusions. All five patients with ependymoma who received 5-AZA infusions had progressive disease. Two of the five patients, however, were noted to have decrease in the size of at least one intraventricular lesion.Conclusion5-AZA can be infused into the fourth ventricle or posterior fossa tumor resection cavity without causing neurological toxicity. Future studies with higher doses and/or increased dosing frequency are warranted.