RSR13 ADMINISTERED TO PATIENTS RECEIVING CRANIAL RADIATION THERAPY

RSR13是一种人工合成的血红蛋白变构修饰剂。它降低了血红蛋白的氧亲和力，增加了微血管中的氧卸载，从而增加了氧向组织的扩散梯度。通过增加组织氧合，RSR13可能会减少肿瘤缺氧，并增强放射治疗用于治疗实体瘤癌症患者的细胞毒效应。为了测试RSR13的安全性、耐受性和最大耐受重复剂量，我们对接受多形性胶质母细胞瘤常规六周颅脑放射治疗的患者进行了一项非随机、开放标签、多中心的安全性研究。参加这项研究的患者有经组织学证实的幕上IV级星形细胞瘤(多形性胶质母细胞瘤)。RSR13的剂量为100 mg/kg，浓度为20 mg/mL，经中心静脉插管持续输注60min以上。RSR13给药在放射治疗的第一天开始，并在放射治疗开始前30分钟内结束输液。使用两个剂量频率组，A组和B组，每组9人。A组隔日给予RSR13 100 mg/kg，B组每日给予RSR13 100 mg/kg。

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.