A phase I study of prolonged ambulatory infusion of ifosfamide with oral mesna

Abstract

<h4>Background</h4>Oral mesna allows investigation of ifosfamide as a prolonged ambulatory infusion for dose-intense out-patient use.<h4>Methods</h4>Cohorts of 3 patients received escalating doses of ifosfamide from 200 to 1,000 mg/m2/day as continuous ambulatory infusion with oral mesna at 30% of the ifosfamide dose every 6 h commencing 2 h prior to ifosfamide infusion as uroprotection on a 14-day schedule with cycles repeated every 28 days.<h4>Results</h4>Fifteen patients received a median of three cycles. Dose-limiting toxicities with cycle 1 were lethargy and hepatotoxicity at 1,000 mg/m2/14 days. Transient transaminase elevation was seen at all dose levels. The other grade 3 toxicities were single episodes of anaemia, granulocytopenia, nausea and hypotension. The best response was stable disease in a patient with thyroid cancer.<h4>Conclusion</h4>Ambulatory infusion of 600 mg/m2 ifosfamide with 180 mg/m2 oral mesna was considered suitable for phase II trials and delivers dose-intense out-patient therapy without urotoxicity.