CLINICAL APPLICATION OF CHRONOBIOLOGY TO CANCER MEDICINE

时间生物学在癌症医学中的临床应用

• 批准号: 3169732
• 负责人: WILLIAM JM HRUSHESKY
• 金额: $ 25.74万
• 依托单位: ALBANY MEDICAL COLLEGE
• 依托单位国家: 美国
• 财政年份: 1982
• 资助国家: 美国
• 起止时间: 1982-03-01 至 1996-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3169732
• 关键词: antineoplastics; behavior; circadian rhythms; diagnosis design /evaluation; dosage; drug administration routes; drug adverse effect; evaluation /testing; floxuridine; human subject; human therapy evaluation; kidney neoplasms; neoplasm /cancer chemotherapy; patient /disease registry; purine /pyrimidine metabolism; sleep

It is proposed to continue to investigate whether the application of circadian time-based chemotherapy can minimize drug toxicity and maximize its anticancer activity. This work will focus entirely upon the study of the circadian timing of infusional fluoropyrimidine chemotherapy. A multi-center clinical study utilizing single agent fluorodeoxyuridine will be performed in patients with metastatic progressive measurable renal cell carcinoma (RCC). This application expands the clinical study of chronopharinacodynamic questions from Albany Medical College to five additional centers with great independent interest in fluoropyrimidine chronopharmacology and/or kidney cancer. Dr. Robert Diasio at the University of Alabama in Birmingham, Dr. Robert Huben at Roswell Park Memorial Institute, Dr. Ace Allen at the University of Kansas, Dr. Georg Bjarnason at the Toronto-Bayview Hospital and Dr. Elwin Fraley at the University of Minnesota have each pledged to participate in the proposed study. Good performance status, previously untreated patients with measurable, progressive, metastatic RCC will be studied using a two-armed design which randomly assigns circadian infusion pattern. Based upon extensive preclinical murine and clinical phase I and phase II study of infusional FUDR in nearly 250 patients this agent will be delivered either by standard 14-day constant rate infusion or multi-step quasi-sinusoidal infusion peaking between 8 p.m. and 2 a.m. each day, repeated every 28 days. Because of well documented inter-individual differences in fluoropyrimidine tolerance and because of the likely importance of fluoropyrimidine dose intensity each study will employ individual FUDR dose escalation, allowing each evaluable patient to receive her or his highest safely tolerated fluoropyrimidine dose intensity. This clinical study will test the effect of circadian infusion shape upon: drug toxicity; maximum tolerated dose; mean dose intensity; frequency, quality and duration of tumor response; and patient survival.

建议继续调查是否应用 昼夜节律的化疗可以最大程度地减少药物毒性并最大化 它的抗癌活性。 这项工作将完全集中于研究 输注氟吡啶化疗的昼夜节律时间。 一个 多中心的临床研究利用单药氟羟基尿苷将 在具有转移性进行性测量肾细胞的患者中进行 癌（RCC）。 该应用扩展了 从奥尔巴尼医学院到五个 对氟嘧啶的独立感兴趣的其他中心 年流制药和/或肾癌。 罗伯特·迪亚西奥博士在 阿拉巴马大学伯明翰，罗斯威尔公园的罗伯特·豪本博士 纪念研究所，堪萨斯大学的Ace Allen博士，乔治博士 多伦多 - 巴伊维尤医院的Bjarnason和Elwin Fraley博士在 明尼苏达大学分别承诺参加拟议的 学习。 良好的表现状态，以前未经治疗的患者 将使用两臂的可测量，进行性转移RCC研究 随机分配昼夜节律输液模式的设计。 基于 广泛的临床前鼠和临床I期以及II期研究 近250名患者的输液FUDR该代理人将被交付 按标准的14天恒定速率输注或多步准螺体 下午8点之间的输液达到峰值每天凌晨2点，每28次重复一次 天。 由于有良好的个人间差异 氟嘧啶的耐受性，并且由于可能的重要性 氟嘧啶剂量强度每项研究将采用单个FUDR剂量 升级，允许每个可评估的患者收到她或他的最高 安全耐受的氟嘧啶剂量强度。 这项临床研究将 测试昼夜节律形状对：药物毒性的影响；最大限度 耐受剂量；平均剂量强度；频率，质量和持续时间 肿瘤反应；和患者的生存。