HUMAN CLINICAL STUDIES

羟色胺临床应用的研究进展 由于缺乏一个准确的定量系统， 描述不均匀的加热模式， 不可避免地导致人类患者，以及可靠性问题， 为大面积浅表和深部位提供足够的动力 肿瘤的尽管存在这些困难，但最近有三个欧洲阶段报告， III期临床试验显示，缓解率、局部控制和 与单纯放疗相比，热放疗的生存率。这些 结果已经在小的，容易接近的表面上完成， 肿瘤，与不精确的知识的温度分布， 实际上已经实现了。我们的论点是有效的应用 然而，在更广泛的实体癌中， 这取决于证明热疗可以 以一种与治疗相关的可验证的定量方式， 结果。 在该项目中，提出了四项人体临床试验：l）两项人体临床试验， 浅表肿瘤和软组织肉瘤的治疗方案 提出了前瞻性测试剂量学概念，2）计算机 RF阵列器件的相移和幅移的仿真将被 经过测试，可优化功率沉积并提高温度 在深部盆腔肿瘤中，3）腹膜内注射的I-II期试验 顺铂和局部HT联合钠盐化疗 硫代硫酸盐作为肾保护剂，用于治疗晚期 复发性卵巢癌 从前瞻性剂量建立剂量-效应关系 升级研究可以有多种益处。剂量-效应关系 将允许更合理的设备设计和测试。它还将 制定了热放疗实践标准， 作为设计和实施III期试验的基础。 IP顺铂最大耐受剂量的确定，当 结合局部热疗， 这种联合疗法的第二阶段测试正在进行的I期临床 我们已经超过了假设中设定的剂量。 研究（MTD >80 mg/m2）。因此，计划将执行第二阶段， 一旦第一阶段研究完成。

Progress in the development of HT as a clinically useful therapeutic modality has been retarded by lack of an accurate and quantitative system of thermal dosimetry to describe the non -uniform heating patterns that invariably result in human patients, as well as problems in reliably delivering adequate power to large superficial as well as deep seated tumors. Despite these difficulties, three recently reported European phase III trials have demonstrated improved response rates, local control and survival for thermoradiotherapy as compared with radiation alone. These results have been accomplished in small, easily accessible superficial tumors, with imprecise knowledge of the temperature distributions that were actually achieved. It is our contention that efficacious application of hyperthermia to the broader scope of solid cancers, however, is dependent upon demonstrating that hyperthermic treatment can be prescribed in a verifiable and quantitative fashion that correlates with treatment outcome. In this project, four human clinical trials are proposed: l) two human protocols for the treatment of superficial tumors and soft tissue sarcomas are proposed which prospectively test dosimetric concepts, 2) computer simulations of phase and amplitude shifting of RF array devices will be tested as a means to optimize power deposition and increase temperatures in deep seated pelvic tumors, 3) phase I-II testing of intraperitoneal chemotherapy with cisplatinum and regional HT, combined with sodium thiosulfate as a renal protective agent, for the treatment of advanced recurrent ovarian cancer. The establishment of dose-effect relationships from prospective dose escalation studies can have multiple benefits. Dose-effect relationships would allow for more rationale equipment design and testing. It would also establish standards for practice of thermoradiotherapy, which could be used as a basis for the design and implementation of phase III trials. The determination of maximally tolerated dose of IP cisplatin, when combined with regional hyperthermia will allow us to move forward with phase II testing of this combined therapy. In an ongoing Phase I clinical trial we have already exceeded the dose set forward in the hypothesis of the study (MTD >80 mg/m2). Thus, the plan will be to implement phase II as soon as the phase I study is completed.