The long-term objective of this multidisciplinary program is to develop improved therapy for advanced or refractory human cancer using hyperthermia (HT) to potentiate effects of radiation therapy (RT) and chemotherapy. The rationale of these therapeutic combinations is that HT can produce direct cytotoxicity, can produce thermoradiosensitization, can markedly enhance effects of many standard chemotherapeutic agents, and can reverse acquired cellular resistance to drugs such as cisplatin. Unique aspects of the program include complementary studies in canines with spontaneous neoplasia and humans through combined resources of Duke University and the North Carolina State University College of Veterinary Medicine. Thermal dosimetry is a theme of the program, as is study of blood perfusion effects on cellular metabolism, temperature distributions, and drug distribution.
Specific aims addressed in 5 projects (P) include: PI: Testing combined local plus systemic HT as a method of improving efficacy of HT + RT relative to local HT + RT alone using Phase I/II trials in canines with soft tissue sarcoma. PII: Evaluating systemic therapy strategies combining whole body HT with cisplatin, carboplatin, and new platinum-dye compounds using extensive pharmacokinetic studies in rats and canines (Phase I and II) and evaluating combined IP/IV cisplatin administration plus regional HT in canines as a model for improved therapy to the intraabdominal compartment, PIII: Testing ability of phase and amplitude controlled microwave systems to heat deep tumors invasively and noninvasively in human Phase I trials; testing strategies for improving heating of superficial human tumors in Phase I/II trials; testing strategies for improving heating of superficial human tumors in Phase I/II trials; and testing the use of intraperitoneal cisplatin plus regional HT for advanced ovarian carcinoma in Phase I/II studies, PIV: Developing and testing methods for reconstructing 3-dimensional temperature fields using numerical modeling supplemented with sensitivity analyses, phantom measurements, and in vivo measurements, and PV: Developing methods to assess prognosis, monitor therapy results, and improve therapeutic efficacy using magnetic resonance imaging (MRI) and spectroscopy methods in canines and humans. These projects are supported by administrative, animal, biostatistics, and engineering cores. The latter provides quality assurance for clinical trials, development of improved HT equipment, support of numerical modeling studies, and development of noninvasive temperature measurements using MRI.
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