Ifosfamide and etoposide are superior to vincristine and melphalan for pediatric metastatic rhabdomyosarcoma when administered with irradiation and combination chemotherapy: A report from the Intergroup Rhabdomyosarcoma Study Group

Purpose: This study was designed to estimate the partial and complete respo nse rates (CR and PR) of two novel drug pairs (vincristine and melphalan vs . ifosfamide and etoposide) and to improve overall survival of previously u ntreated patients with metastatic rhabdomyosarcoma. Patients and Methods: One hundred twenty-eight patients were randomly assig ned to phase II window therapy consisting of vincristine and melphalan (VM- containing regimen) or ifosfamide and etoposide (IE-containing regimen). Br ief window therapy (12 wks) was immediately followed-up by vincristine, dac tinomycin, and cyclophosphamide (VAC), chemotherapy, surgery, and irradiati on, with continuation of either VM or IE in patients with initial response. Major endpoints were initial CR and PR rates after the phase II window pha se of therapy, failure-free survival (FFS), and survival. Results: Patients who received the VM-containing regimen experienced signif icantly more anemia, neutropenia, thrombocytopenia, and had more cyclophosp hamide dose reductions. The initial PR and CR rates were not significantly different for patients treated with either regimen (VM, 74%; IE, 79%; P = 0 .428). However, FFS and overall survival (OS) at 3 years were signifi cantl y better with the IE-containing regimen (FFS: 33% vs. 19%; P = 0.043; OS: 5 5% vs. 27%; P = 0.012). Conclusions: Although the VM-containing regimen produced a high response ra te, inclusion of melphalan appeared to limit the cyclophosphamide dose that could be administered, and ultimately, this regimen was associated with a significantly worse outcome than was the IE-containing regimen. Also, the I E-containing regimen was associated with a gratifyingly high survival rare at 3 years (55%), which is significantly higher than has been observed on a ny previous Intergroup Rhabdomyosarcoma Study Group regimen for similar pat ients. We believe that this promising outcome indicates that this drug pair merits further randomized testing in metastatic rhabdomyosarcoma.