PERITUMORAL BRAIN EDEMA IN PATIENTS WITH MALIGNANT BRAIN TUMOR

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。假设：人促肾上腺皮质激素释放因子(HCRF)可部分或全部替代地塞米松治疗瘤周脑水肿。目的：皮质类固醇(主要是地塞米松)用于治疗脑肿瘤及其相关的瘤周脑水肿已有30多年的历史，尽管长期使用和大剂量使用会产生严重和有害的内分泌影响。这些影响包括严重的肌病、肌肉萎缩、病态体重增加、骨质疏松症、胃肠道出血和个性改变。最近的实验结果也表明，地塞米松干扰恶性胶质瘤细胞的凋亡死亡，从而诱导对常用的化疗和放射治疗的抵抗。本研究的目的是观察hCRF在需要长期应用大剂量地塞米松以控制瘤周脑水肿体征和症状的恶性脑肿瘤患者中的安全性和有效性。实验设计：200名患者随机分为两个治疗组，将参与这项双盲、安慰剂对照研究。患者随机分组的标准是：原发或转移性肿瘤、基线的开放标签地塞米松剂量(每天8、8-16或17-24毫克)以及卡诺夫斯基绩效评分(50-70或80-100)。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Hypothesis: Human corticotropin-releasing factor (hCRF) can partially or totally replace Dexamethasone for the treatment of peritumoral brain edema. Goals: Corticosteroids (predominantly Dexamethasone) have been used in the treatment of brain tumors and associated peritumoral brain edema for more than 30 yrs despite the severe and detrimental endocrine effects associated with long-term use and high doses. Among these effects are severe myopathies, muscle wasting, morbid weight gain, osteoporosis, gastrointestinal bleeding, and personality changes. Recent experimental findings also indicate that Dexamethasone interferes with apoptotic death of malignant glioma cells, and thereby induces resistance to commonly used chemotherapies and radiation therapy. The objective of this study is to examine the safety and efficacy of hCRF in patients with malignant brain tumor who require chronic administration of high dose Dexamethasone to control signs and symptoms of peritumoral brain edema. Experimental Design: Two hundred patients, randomized to one of two treatment groups, will participate in this double-blind, placebo-controlled, study. Patient randomization will be stratified by: primary or metastatic tumor, open-label Dexamethasone dose at baseline (4-<8, 8-16 or 17-24 mg/day), and Karnofsky Performance Scale (50-70 or 80-100).