A Phase I Study of Prolonged Ambulatory Infusion of Ifosfamide with Oral Mesna

Abstract

Background: Oral mesna allows investigation of ifosfamide as a prolonged ambulatory infusion for dose-intense out-patient use. Methods: 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. Results: 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. Conclusion: 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.

The cytogenetic action of ifosfamide, mesna, and their combination on peripheral rabbit lymphocytes: an in vivo/in vitro cytogenetic study

“…However, in spite of its successful anticancer action, the increased toxicity presented in healthy tissues and particularly in the renal and the bladder epithelium, led to its restricted usage and administration. This pressing issue was overcome with the development of mesna acting in an antioxidant fashion, was proven to successfully protect from the running risk of emergence of hemorrhagic cystitis as well as from other side effects of IFO (Anderson 2010;Ichiki et al 2003;Olver et al 2005). IFO is a well known and widely applied anticancer substance but it also has cytotoxic effects.…”

“…Mesna is extensively applied during chemotherapy, along with IFO and in combination with other chemotherapeutic factors, in order to decrease the toxic action of the drugs and eliminate or minimize certain side effects (Olver et al 2005;Hogle 2007;Okayasu et al 2009;Anderson 2010). Moreover, mesna shields human cultured lymphocytes from the cytotoxic action of cyclofosfamide and its derivatives (Wilmer et al 1986b;Mourelatos et al 2012b).…”