ICE (IFOSFAMIDE, CARBOPLATIN, ETOPOSIDE) CHEMOTHERAPY AND SYSTEMIC HYPERTHERMIA

Preclinical studies are consistent with the concept that 41.8 degrees C whole body hyperthermia (WBH) can enhance the therapeutic index of a ntineoplastic agents. These laboratory investigations resulted in four phase I/II clinical studies, which also support this hypothesis. Thes e studies were extended to sin phase II and one phase III investigatio ns of WBH plus ifosfamide. carboplatin and etoposide (ICE) for patient s with metastatic and/or refractory sarcoma, ovary cancer, breast canc er, non-small cell lung cancer. head and neck cancer and malignant mel anoma. Only patients (14-65 fears of age) with (h)istologically confir med advanced cancer beyond hope for surgical cure or metastatic diseas e have been treated. AU patients hal-e had a projected life expectancy of at least 12 weeks and a WHO performance status of 0, 1 or 1. WBH ( 41.8 degrees C for 60 min) with ICE chemotherapy IFO (5 g/m(2)), CBDCA (300 mg/m(2)) and VP-16 (given with WBH, as well as day 2 and 3 post WBH at 100 mg/m(2)) was given every 3 weeks. All patients received fil grastim post ICE/WBH. nle response rates in our multi-institutional tr ials remain quilt high at approximate to 40% (refractory sarcoma). res pectively approximate to 60% (de-novo-/metastatic sarcoma). The degree of bone marrow toxicity seen with radiant heat WBH/ICE vs. ICE alone is essentially identical. On average. 50% of patients exhibit grade II I/IV anemia; 90% experienced grade III/IV neutropenia or thrombocytope nia. No cardiopulmonary toxicity has been observed. The former problem of renal toxicity has been essentially eliminated. Taken collectively the laboratory and clinical investigations of the member institutions of the Systemic Hyperthermia Oncological Working Group (SHOW Group) h ave evolved a potentially new and therapeutically sound therapy for ma lignant sarcoma and other solid tumors.