Pharmacokinetics and efficacy of ifosfamide or trofosfamide in patients with intraocular lymphoma

Abstract

Background: The prognosis of intraocular lymphoma (IOL) is poor, and the optimal treatment has not yet been defined. The study assesses ifosfamide (IFO) and trofosfamide (TRO) for treating IOL. Patients and methods: We prospectively evaluated the efficacy and aqueous penetration of intravenous IFO, oral TRO and their active 4-hydroxy (4-OH) metabolites in 10 patients with IOL. Doses varied from 1500 to 2000 mg/m2/day on days 1-3 for IFO and from 150 to 400 mg/day (continuous or intermittent administration) for TRO. Four patients had newly diagnosed disease, and six had relapsed after pretreatment. Results: All patients responded to first treatment with IFO or TRO, and both of two patients responded to re-treatment with IFO on ocular relapse. Progression-free survival from the first treatment with IFO or TRO was ≥6-18 months. In six of six patients, 4-OH metabolites were detected in the aqueous humor at a concentration of 0.32-1.56 μM immediately after IFO infusion with an aqueous/serum ratio of 0.19-0.54. 4-OH metabolites could be detected in one of three patients at a concentration of 7.2 μM 3-16 h after ingestion of TRO. Conclusions: IFO and TRO are active in IOL. IOL patients evidence aqueous penetration of 4-OH metabolites after intravenous administration of IFO. © 2005 European Society for Medical Oncology.