AMBULATORY HIGH-DOSE 5-DAY CONTINUOUS-INFUSION IFOSFAMIDE COMBINATION CHEMOTHERAPY IN ADVANCED SOLID TUMORS - A FEASIBILITY STUDY

The oxazaphosphorine analog ifosfamide (IFO) has demonstrated an increased therapeutic index in a variety of solid tumors and hematologic malignancies compared with its parent compound cyclophosphamide. A fractionated dose schedule over 5 days as continuous infusion in combination with the uroprotective agent sodium-2-mercapto-ethane-sulfonate (mesna) is considered to provide an improved therapeutic/toxic ratio. Stability data of IFO demonstrate long-term stability for use in disposable infusion pumps as outpatient treatment. In all, 52 patients with various malignancies were entered in a feasibility study to receive outpatient continuous infusion of IFO. All patients were required to have a subcutaneous venous port system implanted. The following drug combinations were used: IFO as single agent, IFO/mitoxantrone, IFO/carboplatinum/etoposide, IFO/etoposide/MTX, IFO/epirubicin. Mitoxantrone and epirubicin were given as continuous infusion together with IFO. Starting dose of IFO was between 1.6-2.0 g/m2/day x 5 and was increased in absence of major hematologic or peripheral toxicity. Mesna was given in combination with IFO as continuous infusion at a dose of 50% of that calculated for IFO. No renal, bladder or central nervous system toxicity was observed. In 247 courses of outpatient continuous ifosfamide infusion only few technical complications due to improper handling were documented.