Ifosfamide with mesna uroprotection and etoposide in recurrent, refractory acute leukemia in childhood: A pediatric oncology group study

Background. Ifosfamide has previously been shown to be active as a single agent and in combination with doxorubicin, etoposide, and teniposide in pediatric solid tumors and adult acute leukemia. The authors performed a dose‐escalation trial of ifosfamide with a fixed dosage of etoposide, with mesna uroprotection, in children with multiply recurrent acute leukemia. Methods. Chemotherapy was administered daily for 5 days. Etoposide 100 mg/m² was followed by ifosfamide at an initial dosage of 1.6 g/m². The ifosfamide was escalated in 20% increments to the maximum tolerated dosage in cohorts of three patients. Mesna 400 mg/m² was given immediately before the ifosfamide and then at 3 and 6 hours after ifosfamide in the initial patients. Subsequent patients were treated with mesna 400 mg/m² just before ifosfamide, and then every 2 hours to a total dosage equal to the ifosfamide dosage. Results. Forty‐four heavily pretreated patients were entered on study. Forty were evaluable for toxicity and 36 for response as well. The maximum tolerated dosage of ifosfamide was 4.0 g/m²/d for 5 days (20 g/m²/course). Overall, 10 patients achieved complete remission, and 3 achieved partial remission. Remissions were brief, although four patients went on to bone marrow transplant while in remission. One patient is still alive. Conclusions. The combination of etoposide and ifosfamide with mesna uroprotection showed promising activity in children with multiply recurrent acute leukemia.