Ifosfamide in pediatric malignancies.

In pediatric malignancies, particularly sarcomas, alkylating agents play an important role in the curative, combination chemotherapy approach. Since high doses of ifosfamide, the structural isomer of cyclophosphamide, were made tolerable with mesna uroprotection, high-dose ifosfamide (5 to 10 g/m2) has replaced conventional-dose cyclophosphamide (900 to 1,500 mg/m2) in some combination chemotherapy regimens. In Ewing's sarcoma and soft tissue sarcoma, the response rate and proportion of patients surviving disease free have been increased (at least for poor-prognosis patients) by 15% to 20% with an ifosfamide-containing regimen, as used in ongoing trials of the German Society of Pediatric Oncology. In germ cell tumors, the combination of ifosfamide and etoposide has proved to be an effective salvage regimen in patients resistant to vinblastine, bleomycin, and cisplatin. In stage IV disseminated neuroblastoma, however, the introduction of ifosfamide-containing regimens has not altered the poor prognosis. Results reflecting the value of ifosfamide in osteosarcoma, Wilms' tumor and Hodgkin's and non-Hodgkin's lymphomas are pending. It is not yet known whether high doses of akylating agents will increase the risk of late sequelae in cured patients.