PERITUMORAL BRAIN EDEMA IN PATIENTS WITH MALIGNANT BRAIN TUMOR

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。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：30多年来，皮质类固醇（主要是地塞米松）一直被用于治疗脑肿瘤和相关的瘤周脑水肿，尽管长期使用和高剂量会对内分泌产生严重和有害的影响。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、胃肠道出血和人格改变。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，从而诱导对常用化疗和放疗的耐药性。本研究的目的是检查hCRF在恶性脑肿瘤患者中的安全性和有效性，这些患者需要长期给予大剂量地塞米松来控制肿瘤周围脑水肿的体征和症状。实验设计：200名患者，随机分为两个治疗组之一，将参加这项双盲，安慰剂对照的研究。患者随机分组将根据：原发或转移性肿瘤、开放标签地塞米松基线剂量（4-< 8,8 -16或17-24 mg/天）和Karnofsky表现量表（50-70或80-100）进行分层。

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).