Systemic therapy for osteosarcoma and Ewing sarcoma.

Curative therapy for both osteosarcoma and Ewing sarcoma requires the combination of effective systemic therapy and local control of all macroscopic tumors. Systemic therapy for osteosarcoma consists of multiagent chemotherapy. The most common regimen uses cisplatin, doxorubicin, and high-dose methotrexate. Addition of ifosfamide and etoposide to treatment for patients with poor initial response to therapy does not improve outcome. Addition of interferon to treatment for patients with favorable initial response does not improve outcome. Addition of liposomal muramyl tripeptide to chemotherapy may improve overall survival. Systemic therapy for Ewing sarcoma consists of multiagent chemotherapy including doxorubicin, vincristine, etoposide, and cyclophosphamide and/or ifosfamide. Increased dose intensity of therapy, either by shortening the intervals between cycles of chemotherapy or by increasing doses of chemotherapy, improves outcome. Regimens such as irinotecan/temozolomide or cyclophosphamide/topotecan have shown activity in metastatic recurrent Ewing sarcoma. Trials are ongoing to evaluate the addition of these drugs to existing multiagent regimens in order to test their ability to improve outcome. High-dose systemic therapy with autologous stem cell reconstitution is being tested for patients at high risk for recurrence; definitive results await completion of a prospective randomized trial.