High-dose alkylation therapy using ifosfamide infusion with mesna in the treatment of adult advanced soft-tissue sarcoma

In a phase II study, 42 patients with advanced soft-tissue sarcoma were treated with ifosfamide by 24-h infusion and mesna by 4-h IV bolus, repeated every 3 weeks. Ten patients received ifosfamide 5.0 g/m2, 20 had the dosage increased to 8.0 g/m2, and 12 received 8.0 g/m2 from the outset. Mesna was given in doses of 400 mg/m2 or 600 mg/m2. Of 40 patients evaluable for response, six (15%) achieved complete response and nine (23%) partial response. The overall response rate was 38%. The median duration of response was 11 months. Treatment was associated with falls in peripheral WBC and alopecia in all patients. Most experienced severe nausea and vomiting. In seven nephrotoxicity developed, and two of these died of renal failure. Renal tubular defects and cerebral effects also occurred. Mesna largely prevented haemorrhagic cystitis. Ifosfamide offers a new alternative to previous chemotherapy for advanced soft-tissue sarcoma, but alterations in dose or method will be necessary to reduce toxicity.