IN VITRO STUDIES OF SURAMIN NEUROTOXICITY

苏拉明神经毒性的体外研究

• 批准号: 3416657
• 负责人: ANTHONY John WINDEBANK
• 金额: $ 12.36万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-04-01 至 1995-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3416657
• 关键词: biopsy; clinical trials; computer assisted diagnosis; diagnosis design /evaluation; drug adverse effect; electromyography; human subject; human therapy evaluation; metastasis; neoplasm /cancer chemotherapy; neoplasm /cancer classification /staging; nervous system disorder diagnosis; neuromuscular disorder diagnosis; neurotoxins; peripheral nervous system disorders; prostate neoplasms; suramin; tissue /cell culture

Sodium suramin is a promising chemotherapeutic agent with possible efficacy against prostate and adrenal cancer. It is being used in phase II trials for patients with advanced D2 cancer of the prostate in a multicenter trial. One of the major adverse effects observed in preliminary trials was a severe peripheral neuropathy. In the studies proposed, patients entered into clinical trials of suramin will be studied prospectively to identify the appearance of peripheral nerve injury. Sensitive quantitative techniques (Neuropathy Symptom Score, Neurologic Disability Score, Computer Assisted Sensory Examination, Nerve Conduction Studies, Needle Electromyography, and Quantitative Autonomic Examination) will be used at baseline and at intervals during therapy. The characteristics of the neuropathy in terms of fiber class loss and fiber pathology (axonal degeneration versus demyelination) will be determined by study of nerve biopsy. Weekly estimation of serum suramin will allow correlation of development of neuropathy with duration and level of exposure to the drug. This adverse effect will be compared to tumor regression to determine if a therapeutic window exists. Those patients developing neuropathy will be studied for 12 months following cessation of therapy to determine whether the neuropathy is reversible.

苏拉明钠是一种很有前途的化疗药物 对前列腺癌和肾上腺癌的疗效。它正被用于 晚期D2前列腺癌患者的II期试验 在一个多中心试验中。观察到的主要不良反应之一是 初步试验是一种严重的周围神经病变。在 研究建议，患者进入苏拉明的临床试验 将进行前瞻性研究，以确定 周围神经损伤。灵敏的定量技术 (神经病症状评分、神经功能障碍评分、计算机 辅助感觉检查，神经传导研究，针灸 肌电图术和定量自主神经检查) 在基线和治疗期间每隔一段时间使用。这个 神经病的纤维类丢失和神经病变特征 纤维病理学(轴突变性与脱髓鞘)将是 由神经活检研究确定。每周一次的血清评估 苏拉明将允许神经病变的发展与 接触药物的时间和程度。这一不利影响将 与肿瘤消退进行比较，以确定一个治疗窗口 是存在的。那些出现神经病变的患者将被研究12年 在停止治疗后几个月，以确定是否 神经病是可逆的。