Reduction of Ifosfamide Toxicity Using Dose Fractionation1

the genitouninamy system. Itostamide has been found to produce hemorrhagic cystitis in 40 to 50% of the patients receiving the drug in single high doses (7, 9, ii). This type of toxicity is accompanied by dysunia and frequency. Azo temia also has been observed in patients receiving doses of 150 mg/kg (11). Cardiac toxicity has not been reported with doses of Ifostamide used to date. Because of the potential importance of Ifosfamide in can cemchemotherapy, a study was conducted in which the total dose of Ifosfamide was fractionated in an attempt to reduce the limiting toxicity while preserving the therapeutic efti cacy. We postulated that if bladder and renal toxicity were due to the effects of large amounts of alkylating substances in the urine (9), the amount of such substances could be reduced by fractionating the total dose in multiple days of administration. Thus, a schedule was designed in which Ifosfamide was administered in a 5-day period instead of in 1 day and each iv. administration was given for 1 to 2 hr instead of iv. bolus. The objectives of this study were to determine the maximum tolerated dose of Ifosfamide ad ministered in intermittent S-day courses, to determine the qualitative and quantitative toxicity of Ifosfamide adminis tered in this fashion, and to investigate the therapeutic effect in patients with advanced malignant diseases.