Experience with ifosfamide in the EORTC Soft Tissue and Bone Sarcoma Group

The Soft Tissue and Bone Sarcoma Group of the European Organization on Research and Treatment of Cancer has conducted a number of studies of chemotherapy in advanced disease over the past 15 years. Following the discovery that the CYVADIC regimen (cyclophosphamide/vincristine/doxorubicin/dimethyl imidazole carboxamide) was less active than had been reported originally, the individual components of CYVADIC were studied. This showed that doxorubicin had considerable activity and that ifosfamide 5 g/m2 given over 24 hours was at least as active as cyclophosphamide. Subsequent studies have therefore centered on a combination of doxorubicin and ifosfamide. A large randomized trial showed no significant benefit of doxorubicin/ifosfamide over single-agent doxorubicin, but the doses of doxorubicin were different. More recently, using bone marrow growth factors, it has been possible to increase the doxorubicin dose to that given as a single agent and also maintain the ifosfamide dose. This is now being tested in a randomized trial to determine whether improved response rates and other indicators of outcome will be seen.