FLUOSOL AND HBO AS ADJUNCTS TO RADIATION THERAPY

FLUOSOL 和 HBO 作为放射治疗的辅助药物

• 批准号: 3181479
• 负责人: JAMES J FISCHER
• 金额: $ 18.06万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-07-15 至 1989-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3181479
• 关键词: glioblastoma multiforme; head /neck neoplasm; hemoglobin; human subject; hyperbaric oxygen therapy; hypoxia; ionizing radiation; neoplasm /cancer radiation therapy; radiation dosage; radiation sensitivity

It has been postulated that a possible cause of failure of radiation to produce local tumore control is the existence within tumors of hypoxic cells of reduced radiosensitivity. Fluosol infusion and hyperbaric oxyten breathing will be investigated as a means to overcome this problem by improving the oxygenation of tumor cells during radiation therapy. Theoretical considerations suggest that hyperbaric oxygen alone should be only minimally effective in improving the results of radiation therapy, as has been observed in many clinical trials. Oxygen moves into tissue primarily by diffusion. In order to increase the effective diffusion distance, the partial pressure of oxygen at the capillary level must be significantly increased. This can be accomplished only if sufficient oxygen can be carried in the blood not bound to hemoglobin, so that no unloading of oxygen from hemoglobin is necessary to supply tissue needs. Because of the limited solubility of oxygen in plasma this condition cannot be met with hyperbaric oxygen alone at pressures which are convenient and non-toxic. Fluosol, a perfluorochemical oxygen transport fluid and plasma expander, has been used as a blood substitute and to improve the oxygen carrying capacity of whole blood. In the presence of Fluosol, in concentrations well tolerated in man, the non-hemoglobin oxygen carrying capacity of blood will be sufficient at elevated oxygen pressure to overcome the oxygen buffering capacity of hemoglobin. Hyperbaric oxygen augmented by Fluosol should increase oxygen partial pressure at the capillary level, increase tumor oxygenation and thereby improve the results of radiation therapy. Preliminary animal studies support these predictions. Two specific clinical trials based on this hypothesis are proposed: 1) a phase I-II trial to investigate the safety and efficacy of the addition of Fluosol and hyperbaric oxygen breathing to radiation therapy in the treatment of advanced unresectable squamous cell carcinoma of the head and neck region, and 2) a phase I-II trial to investigate the safety and efficacy of the addition of FLuosol infusion and hyperbaric oxygen breathing to radiation therapy in the treatment of glioblastoma multiforme.

据推测，辐射失败的一个可能原因是 产生局部肿瘤控制是肿瘤内存在的缺氧 放射敏感性降低的细胞。 氟素输液和高压氧 呼吸将被研究作为一种手段来克服这个问题， 在放射治疗期间改善肿瘤细胞的氧合。 理论上的考虑表明，高压氧单独应该是 在改善放射治疗的结果方面只有最低限度的效果， 已经在许多临床试验中观察到。 氧气进入组织 主要是扩散。 为了增加有效扩散 距离，在毛细管水平的氧分压必须是 显著增加。 只有在足够的情况下才能做到这一点 氧气可以在血液中携带，而不与血红蛋白结合，因此， 从血红蛋白中卸出氧是供应组织需要所必需的。 由于氧在血浆中的溶解度有限， 在方便的压力下单独使用高压氧， 无毒。 Fluosol，一种全氟化学氧传输流体和等离子体 膨胀剂，已被用作血液替代品，并提高氧气 全血的承载能力。 在Fluosol的存在下，在 在人体中耐受良好的浓度，非血红蛋白携氧 血液的容量将足以在升高的氧气压力， 克服血红蛋白的氧气缓冲能力。 高压氧加氟素可增加氧分压 毛细血管水平的压力，增加肿瘤氧合，从而 改善放射治疗的效果。 初步动物研究 支持这些预测。 基于此的两项具体临床试验 提出假设：1）研究安全性的I-II期试验 以及添加Fluosol和高压氧呼吸对 晚期不能切除鳞状细胞癌的放射治疗 头颈部癌，以及2）I-II期试验， 研究添加氟罗索输注的安全性和有效性， 高压氧呼吸对放射治疗的治疗作用 多形性胶质母细胞瘤