HUMAN CLINICAL STUDIES

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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.