6-DAY CONTINUOUS-INFUSION OF HIGH-DOSE IFOSFAMIDE WITH BONE-MARROW GROWTH-FACTORS IN ADVANCED REFRACTORY MALIGNANCIES

Ifosfamide is an analogue of cyclophosphamide active in the treatment of numerous tumours. Although its use by continuous infusion seems to be responsible for less toxicity, differences of efficacy and toxicity , observed according to its doses and schedules of administration. sti ll remain debated. The objective of this study was to assess the toxic ity of high-dose ifosfamide given by continuous infusion over 6 days a nd its therapeutic activity in various advanced tumours. Twenty-six pa tients were treated with 14 g/m(2) ifosfamide, an equal dose of MESNA, and routine granulocyte- or granulocyte/macrophage-colony-stimulating factor during the intercycle. Courses were repeated every 3 weeks unt il disease progression or unacceptable toxicity occurred; 75 cycles we re administered. The mean number of cycles per patient was 3 (range 1- 11). Extrahaematological toxicity was manageable in most patients, WHO grade II or more neurological (5 patients) and renal (5 patients) tox icities occurring in those heavily pretreated with platinum compounds and presenting peritoneal disease. WHO grade III or more neutropenia o ccurred in 60% of cycles, while grade III-IV thrombocytopenia and anae mia were observed in 19% of them. Three partial responses (germ-cell t umour, chondrosarcoma, soft-tissue sarcoma) and one complete response (metastatic osteosarcoma) were assessed, all in patients with tumours refractory or resistant to standard-dose ifosfamide, which underlines the possibility of circumventing the resistance to ifosfamide given in conventional schedules. The present results confirm previous reports of changes in the therapeutic index of ifosfamide according to its dos e and administration schedule.