Ifosfamide and Etoposide in Recurrent Childhood Acute Lymphoblastic Leukemia

Abstract

Purpose The activity of the drug combination ifosfamide and etoposide (VP16) in refractory and relapsed childhood acute lymphoblastic leukemia (ALL) was assessed in a phase II study. Patients and Methods Twenty children with ALL, all heavily pretreated and in bone marrow relapse, were entered on the study. Drugs were given i.v. each day for 5 days at the following doses: ifosfamide 1.8 g/m²/day, VP16 100 mg/m²/day, and MESNA 2,880 mg/m²/day (as a uroprotectant); cycles were repeated every 28 days. At study entry, eight patients were in first relapse (five of whom had failed intensive reinduction regimens), seven were in second relapse, and five were in third relapse. All patients had received cyclophosphamide in regimens before relapse. Results Eight patients (40%; 95% confidence interval 19–64%) achieved complete bone marrow remission with ifosfamide/VP16. Three patients subsequently relapsed in the bone marrow while on ifosfamide/VP 16 therapy. Duration of remission ranged from 21 to 247 days. Treatment was generally well tolerated, with myelosuppression the most common toxicity; fever and neutropenia occurred in 18 of 31 evaluable cycles. Conclusion The combination of ifosfamide/VP16 has significant activity in recurrent and refractory childhood ALL with tolerable toxicity.