IFOSFAMIDE-CONTAINING CHEMOTHERAPY IN EWINGS-SARCOMA - THE 2ND UNITED-KINGDOM CHILDRENS-CANCER-STUDY-GROUP AND THE MEDICAL-RESEARCH-COUNCILEWING TUMOR STUDY

Purpose: to investigate the possibility that the substitution of ifosf amide for cyclophosphamide therapy for Ewing's sarcoma will improve su rvival over that seen in the first United Kingdom Children's Cancer St udy Group (UKCCSG) Ewing's tumor study (ET-I). Patients and Methods: B etween 1987 and 1993, 243 patients (138 men or boys) were entered onto the study The median age was 13.5 years (range, 1.5 to 27 years). The median follow-up was 58 months. Chemotherapy included four courses of vincristine 2 mg/m(2); ifosfamide 9 g/m(2); and doxorubicin 60 mg/m(2 ) administered every 3 weeks. Treatment of the primary tumor was with surgery and/or radiotherapy followed by ifosfamide 6 g/m(2); doxorubic in 60 mg/m(2); and vincristine 2 mg/m(2); with actinomycin D 1.5 mg/m( 2) substituted for doxorubicin after a total dose of 420 mg/m(2). Resu lts: Two hundred one patients had no metastases, One hundred eighteen patients had tumors of the axial skeleton and 125 patients had limb pr imary tumors. The major toxicities were hematologic and infective, but there were no toxic deaths. The overall survival rate was 62% (95% co nfidence interval [CI], 56 to 69) and relapse-free survival (RFS) 56% (95% CI, 49 to 62). For those with no metastases at diagnosis, the RFS rate was 62% and for those with metastases, 23%. Multivariate analysi s showed age and site to have a significant effect on RFS. Pelvic site s had the worst RFS rate of 41%; other axial sites, 55%; and extremity tumors, 73%, Age younger than 10 years had an RFS rate of 86% versus 55% for older patients. The local relapse rate for axial tumors was 20 % and for limb primary tumors was 2.4%, Conclusion: The 5-year surviva l rate of 62% is improved compared with the 44% survival rate achieved in ET-l, This is probably caused by the use of higher doses of ifosfa mide compared with relatively low doses of cyclophosphamide in ET-1. ( C) 1998 by American Society of Clinical Oncology.