Systemic hyperthermia and ICE chemotherapy for sarcoma patients: rationale and clinical status

Preclinical studies are consistent with the concept that 41.8 degrees C whole body hyperthermia (WBH) can enhance the therapeutic index of specific chemotherapeutic agents. These laboratory investigations resulted in 2 phase I clinical studies, which also support this hypothesis. These trials were extended to 2 sequential phase II investigations of WBH plus ifosfamide, carboplatin and etoposide (ICE) for refractory sarcoma patients. The first study (involving 12 patients) using extra-corporeal WBH was prematurely closed to adopt a less toxic WBH technology, i.e., the radiant heat Aquatherm. To date, 12 patients have been accrued to the Aquatherm trial. Projections regarding reduced morbidity were correct. The response rate for ICE/WBH is currently 63%. The review to follow will summarize the results of these trials, as well as the laboratory and clinical data which serve to explicate the dramatic clinical results observed to date.