DOSING AND SIDE-EFFECTS OF IFOSFAMIDE PLUS MESNA

In clinical practice and in most ongoing studies in adult and pediatric tumours, daily short-time infusions of ifosfamide (IFO) on 2-5 consecutive days with cycle doses between 6 g/m2 and 12 g/m2 are used at present. The continuous i.v. infusion of IFO/mesna over 1-5 days is still experimental. Since mesna prevents IFO-induced urotoxicity, the IFO dose could be increased to 16 g/m2 per cycle. As the dose and schedules of IFO/mesna were increased and varied, CNS and renal toxicity became more evident. CNS toxicity seems not to be dependent on i.v., but on oral dosing of IFO. Renal dysfunction and previous administration of cisplatinum predispose for CNS toxicity. The incidence or severity of CNS toxicity does not increase with subsequent courses of IFO i.v. The nephrotoxicity of IFO is dependent on IFO dose, diuresis, mesna dose and whether there has been previous cisplatinum and seems to involve preferentially the tubulus system, leading to 25 cases of Fanconi renal syndrome as published in 1988-1990. Fanconi's syndrome depends on the cumulative IFO dose, the previous administration of nephrotoxic drugs such as cisplatinum and the age of the children. Studies are continuing to determine the least nephrotoxic dose and schedule of IFO plus mesna. Leucopenia and thrombopenia are well-known dose-dependent side-effects of IFO, with similar incidence after i.v. short-time and continuous infusion.