RSR13 ADMINISTERED TO PATIENTS RECEIVING CRANIAL RADIATION THERAPY

RSR13 给予接受颅脑放射治疗的患者

• 批准号: 6113332
• 负责人: JAMES RUFFER
• 金额: $ 2.51万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-12-01 至 1999-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6113332
• 关键词: clinical research; clinical trial phase I; combination cancer therapy; drug screening /evaluation; glioblastoma multiforme; human subject; human therapy evaluation; neoplasm /cancer chemotherapy; neoplasm /cancer radiation therapy; oxygen tension; radiosensitizer

RSR13 is a synthetic allosteric modifier of hemoglobin. It decreases the oxygen affinity of hemoglobin and augments oxygen unloading in the microvasculature which increases the oxygen diffusion gradient to the tissues. By increasing tissue oxygenation, RSR13 may reduce tumor hypoxia and enhance the cytotoxic effects of radiation therapy used to treat cancer patients with solid tumors. To test the safety, tolerance, and maximally tolerated repetitive dose of RSR13, we conducted a non-randomized, open-label, multi-center safety study in patients who received a conventional six-week course of cranial radiation therapy for glioblastoma multiforme. Patients enrolled in this study had a histologically confirmed supratentorial grade IV astrocytoma (glioblastoma multiforme). The dose of RSR13 was 100 mg/kg at a concentration of 20 mg/mL, administered over 60 minutes by continuous infusion via a central venous access device. RSR13 administration began on the first day of radiation therapy and was given so that the end of the infusion occured within 30 minutes prior to the start of radiation therapy. Two dose frequency groups, Groups A and B, with nine patients per group, were used. Patients in Group A received 100 mg/kg RSR13 every other day of radiation therapy, and patients in Group B received 100 mg/kg RSR13 every day of radiation therapy.

RSR 13是血红蛋白的合成变构修饰剂。 它降低了血红蛋白的氧亲和力，增强了微血管系统中的氧卸载，从而增加了氧向组织的扩散梯度。 通过增加组织氧合，RSR 13可以减少肿瘤缺氧并增强用于治疗患有实体瘤的癌症患者的放射疗法的细胞毒性作用。 为了测试RSR 13的安全性、耐受性和最大耐受重复剂量，我们在接受常规6周颅放射治疗的多形性胶质母细胞瘤患者中进行了一项非随机、开放标签、多中心安全性研究。入组本研究的患者经组织学证实为幕上IV级星形细胞瘤（多形性胶质母细胞瘤）。 RSR 13的剂量为100 mg/kg，浓度为20 mg/mL，通过中心静脉接入装置连续输注在60分钟内给药。 在放射治疗的第一天开始RSR 13给药，并在放射治疗开始前30分钟内完成输注。 使用两个剂量频率组，A组和B组，每组9例患者。 A组患者每隔一天接受100 mg/kg RSR 13放射治疗，B组患者每天接受100 mg/kg RSR 13放射治疗。