High-dose ifosfamide in the treatment of advanced soft tissue sarcomas

Ifosfamide, an oxazaphosphorine analogue, is now commonly used in first-line anthracycline-containing regimens for advanced soft tissue sarcomas, based on its demonstrated single-agent activity in previously treated patients. At the Institut Gustave-Roussy, we performed a phase II study of high-dose ifosfamide without hematopoietic support in patients with adult advanced soft tissue sarcomas previously treated with a doxorubicin-based regimen. Our goal was to confirm a dose-response relationship for ifosfamide in soft tissue sarcoma. Ifosfamide was given at a dose of 4 g/m2/d over 3 days by continuous infusion with an equivalent dose of mesna; an additional 4 g/m2 of mesna was given on day 4. Among 36 evaluable patients, we observed no complete responses and 12 partial responses, for an overall response rate of 33%. No patients with leiomyosarcoma responded to treatment, and some histologic subtypes clearly showed better chemosensitivity than others. The major dose-limiting toxicities were hematologic. Our results confirm a dose-response effect for high-dose ifosfamide in soft tissue sarcomas, with a threshold of approximately 10 g/m2.