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 sin gle agent and in combination with doxorubicin, etoposide, and teniposi de in pediatric solid tumors and adult acute leukemia. The authors per formed a dose-escalation trial of ifosfamide with a fixed dosage of et oposide, with mesna uroprotection, in children with multiply recurrent acute leukemia. Methods. Chemotherapy was administered daily for 5 da ys. Etoposide 100 mg/m2 was followed by ifosfamide at an initial dosag e of 1.6 g/m2. The ifosfamide was escalated in 20% increments to the m aximum 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 tre ated with mesna 400 mg/m2 just before ifosfamide, and then every 2 hou rs to a total dosage equal to the ifosfamide dosage. Results. Forty-fo ur heavily pretreated patients were entered on study. Forty were evalu able for toxicity and 36 for response as well. The maximum tolerated d osage of ifosfamide was 4.0 g/m2/d for 5 days (20 g/m2/course). Overal l, 10 patients achieved complete remission, and 3 achieved partial rem ission. Remissions were brief, although four patients went on to bone marrow transplant while in remission. One patient is still alive. Conc lusions. The combination of etoposide and ifosfamide with mesna uropro tection showed promising activity in children with multiply recurrent acute leukemia.