High-Dose Concurrent Mesna Infusion May Interfere with the Antitumor Activity of Ifosfamide

SummaryTwenty-seven patients with advanced or metastatic soft tissue sarcoma were treated with high-dose ifosfamide (5 g/m2), and concomitantly mesna to prevent urothelial toxicity. An overall response rate of 14.8% was observed (4 partial responses). Two different dose levels of mesna and ways of mesna administration were used. In 17 patients, mesna was given as intravenous bolus injections (400 mg/m2) every 4 h. In 10 patients, mesna was given as a high-dose (5 g/m2) continuous concurrent infusion with ifosfamide. In the low-dose mesna group, 4 responders were observed, whereas no responders were found in the high-dose mesna group. Microscopical hematuria was observed in 11 out of 55 courses in the low-dose mesna group and in 3 out of 21 in the high-dose mesna group. Infections requiring antibiotic therapy were observed after 3 courses in 3 patients, all belonging to the low-dose mesna group. These findings indicated that high doses of concurrently administered mesna could reduce the tumor response as well as the urothelial toxicity of ifosfamide treatment. The results prompted an experimental study that examined whether mesna could interfere with the antitumor activity of ifosfamide in L 1210 tumor-bearing mice. Mesna significantly reduced the effect of ifosfamide in this tumor system.