Benesch Martin, Siegler Nele, Hoff Katja von, Lassay Lisa, Kropshofer Gabriele, Müller Hermann, Sommer Constanze, Rutkowski Stefan, Fleischhack Gudrun, Urban Christian
Division of Pediatric Hematology and Oncology, Department of Pediatrics and Adolescent Medicine, Medical University of Graz, Austria.
Anticancer Drugs. 2009 Oct;20(9):794-9. doi: 10.1097/CAD.0b013e32832f4abe.
This retrospective study aimed to evaluate the safety and toxicity of intrathecal liposomal cytarabine (Depocyte) in children and adolescents with refractory or recurrent brain tumors. Nineteen heavily pretreated patients (males, n = 14; females, n = 5; median age at diagnosis 8.5 years; range, 1.4-22 years) were given intrathecal liposomal cytarabine on a compassionate use basis for recurrent refractory medulloblastoma (n = 12), mixed germ cell tumor (n = 2), central nervous system primitive neuroectodermal tumors of the pons (n = 1), anaplastic ependymoma (n = 1), anaplastic oligodendroglioma (n = 1), atypical teratoid rhabdoid tumor (n = 1), or rhabdoid papillary meningioma (n = 1). Eighteen patients received concomitant systemic radiochemotherapy. A total of 88 intrathecal injections of liposomal cytarabine (dose range, 20-50 mg) were administered with concomitant dexamethasone prophylaxis. The median number of doses per patient was four (range, 1-10). Duration of treatment ranged from (1/2) to 10 months. Eleven patients (57.9%) did not show any side effects, whereas eight patients (42.1%) developed side effects related to either chemical arachnoiditis (n = 4) or neurological progression (n = 2). Less typical treatment-related symptoms (e.g. lethargy, ataxia, and slurred speech) were observed in two patients. Treatment with intrathecal liposomal cytarabine was discontinued twice because of side effects. In conclusion, although intrathecal liposomal cytarabine was generally well tolerated, it should be used cautiously and only with dexamethasone prophylaxis in extensively pretreated patients with recurrent brain tumors. Proof of efficacy requires a prospective single-agent phase II study.
这项回顾性研究旨在评估鞘内注射脂质体阿糖胞苷（Depocyte）在难治性或复发性脑肿瘤儿童和青少年中的安全性和毒性。19例经过大量预处理的患者（男性14例，女性5例；诊断时的中位年龄为8.5岁，范围为1.4 - 22岁）在 compassionate use 的基础上接受了鞘内注射脂质体阿糖胞苷，用于复发性难治性髓母细胞瘤（12例）、混合性生殖细胞肿瘤（2例）、脑桥中枢神经系统原始神经外胚层肿瘤（1例）、间变性室管膜瘤（1例）、间变性少突胶质细胞瘤（1例）、非典型畸胎样横纹肌样瘤（1例）或横纹肌样乳头状脑膜瘤（1例）。18例患者同时接受了全身放化疗。共进行了88次鞘内注射脂质体阿糖胞苷（剂量范围为20 - 50mg），同时预防性使用地塞米松。每位患者的中位注射次数为4次（范围为1 - 10次）。治疗持续时间为（1/2）至10个月。11例患者（57.9%）未出现任何副作用，而8例患者（42.1%）出现了与化学性蛛网膜炎（4例）或神经功能进展（2例）相关的副作用。在2例患者中观察到不太典型的与治疗相关的症状（如嗜睡、共济失调和言语不清）。由于副作用，鞘内注射脂质体阿糖胞苷治疗中断了两次。总之，尽管鞘内注射脂质体阿糖胞苷总体耐受性良好，但在经过广泛预处理的复发性脑肿瘤患者中应谨慎使用，且仅在预防性使用地塞米松的情况下使用。疗效验证需要进行前瞻性单药II期研究。
