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: 3181480
• 负责人: JAMES J FISCHER
• 金额: $ 15.6万
• 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/3181480
• 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低氧 放射敏感性降低的细胞。氟化钠输注与高压氧 将研究呼吸作为克服这一问题的一种手段 在放射治疗过程中改善肿瘤细胞的氧合。 理论上的考虑表明，高压氧本身应该是 在改善放射治疗结果方面只有最低限度的有效，因为 已经在许多临床试验中观察到。氧气进入组织 主要是通过扩散。为了增加有效扩散 距离，毛细管水平上的氧气分压必须是 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，不与血红蛋白结合，因此不会 从血红蛋白中卸载氧气是必要的，以满足组织的需要。 由于氧气在等离子体中的溶解度有限，这种情况不能 在方便的压力下单独接触高压氧 无毒。氟溶胶--一种全氟化学氧气输送液体和血浆 膨胀剂，已被用作血液替代品和改善氧气 全血的承载能力。在氟唑醇存在的情况下， 在人体内耐受性良好的浓度，非血红蛋白携氧 在氧气压升高的情况下，血液容量足以 克服血红蛋白的氧气缓冲能力。 氟化吸入高压氧可增加氧分压 毛细血管水平的压力，增加肿瘤的氧合，从而 提高放射治疗效果。初步的动物研究 支持这些预测。在此基础上进行的两项具体临床试验 提出假设：1)一项研究安全性的I-II期试验 加用氟化吸入和高压氧治疗的疗效观察 晚期不能切除鳞状细胞的放射治疗 头颈部癌，2)I-II期试验，以 观察加服氟罗索输液的安全性和有效性。 高压氧呼吸加放射治疗在肺癌治疗中的应用 多形性胶质母细胞瘤。