HUMAN CLINICAL STUDIES

羟色胺作为临床有用治疗药物的研究进展 由于缺乏准确和定量的系统，情态反应迟缓 描述非均匀加热模式的热剂量学 总是会导致人类患者，以及在可靠性方面的问题 向大型、浅表和深层次的用户提供足够的电力 肿瘤。尽管有这些困难，最近报道的三个欧洲阶段 III试验表明，应答率、当地控制率和 与单纯放射治疗相比，热放射治疗的存活率。这些 结果是在小的、容易接近的表面上取得的 肿瘤，由于对温度分布的不精确了解 实际上已经实现了。我们的论点是，有效的应用 然而，高温对更广泛的实体癌症范围的影响是 取决于证明可以开出过热治疗的处方 以与治疗相关的可验证和定量的方式 结果。 在这个项目中，提出了四个人体临床试验：L)两个人 浅表肿瘤和软组织肉瘤的治疗方案 提出了前瞻性地检验剂量学概念，2)计算机 将对射频阵列器件的相移和振幅进行模拟 作为一种优化电源沉积和提高温度的手段进行了测试 对于深层盆腔肿瘤，3)腹膜腔内I-II期检查 顺铂联合局部羟色胺联合钠盐化疗 硫代硫酸盐作为肾脏保护剂治疗晚期糖尿病 复发性卵巢癌。 从预期剂量建立剂量-效应关系 上报研究可能有多个好处。剂量-效应关系 将允许进行更合理的设备设计和测试。它还会 建立热放射治疗实践的标准，这可以是 作为设计和实施第三阶段试验的基础。 Ip顺铂最大耐受量的测定 结合区域体温升高将使我们能够继续 这一联合疗法的第二阶段测试。正在进行的I期临床试验 试验中，我们已经超过了假设中设定的剂量 研究(MTD&GT；80 mg/m2)。因此，计划将实施第二阶段为 一旦我的研究阶段完成。

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.