Protocol therapy will consist of induction, Local control and Consolidation therapy. Protocol therapy must begin only after study enrollment and randomization. all patients, whether in Regimen a or Regimen B will receive a total of 17 cycles of chemotherapy; each cycle will be of 2 weeks duration. induction consists of 6 cycles (12 weeks) of chemotherapy and will be delivered prior to local control therapy which may involve surgery and/or radiation therapy. Consolidation therapy will consist of 11 cycles (22 weeks) of chemotherapy.
Regimen a (Standard arm) will consist of alternating cycles of Vincristine/Doxorubicin/Cyclophosphamide and ifosfamide/etoposide.
Regimen B (experimental arm) will consist of alternating cycles of Vincristine/Doxorubicin/Cyclophosphamide, ifosfamide/etoposide and Vincristine/Topotecan/Cyclophosphamide. Total doses of Doxorubicin will be equal in both arms (375 mg/m2) but slight differences in total dose of other agents will occur: Cyclophosphamide (10.8 gram/m2 Regimen a vs. 12.25 gram/m2 Regimen B), ifosfamide (72 gram/m2 Regimen a vs. 64 gram/m2 Regimen B) and etoposide (4 gram/m2 Regimen a vs. 3.5 gram/m2 Regimen B). Regimen B includes 2 added DoSeS of Vincristine and Topotecan.
outcome variables will include randomized treatment arm, local control modality, primary tumor site, primary tumor volume, surgical margins, histological tumor response, biological tumor markers, FDG positron emission tomography (PeT) avidity. Study end-points will include event-free and overall survival, musculoskeletal complications and treatment related toxicities.
* Age less than or equal to 50 years.
* Patients with newly diagnosed, biopsy confirmed, extracranial, non-metastatic Ewing sarcoma or PNET of bone or soft tissue are eligible for this study.
* Patient eligibility will be based on a diagnosis of Ewing sarcoma or PNET by institutional pathologist.
* No prior chemotherapy or radiation therapy is allowed.
* Adequate renal function
* Adequate liver function
* Adequate cardiac function