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.
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Institut Gustave-Roussy, Paris, France.
D000328:Adult; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage* / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D012509:Sarcoma / Q000188:drug therapy*; D012983:Soft Tissue Neoplasms / Q000188:drug therapy*
D018906:Antineoplastic Agents, Alkylating; D007069:Ifosfamide