Background: Multimodality management of osteosarcoma has significantly improved the 5-year-survival rate for localized disease over the past 40 years: from 5% - 10% (in historical controls) to 65% - 75% and 20% - 30% in metastatic disease. These results were achieved with doxorubicin, cisplatin, high-dose methotrexate and ifosfamide (or cyclophosphamide). In the absence of new and effective agents the results have remained stationary for at least the past 30 years. No standard second line therapy exists for patients who relapse. In these circumstances surgery when feasible, constitutes the main therapeutic option. Questions/Purposes: To understand the present approach to therapy and determine the possibilities for improvement a review of the chemotherapeutic agents currently deployed in the treatment of Osteosarcoma was undertaken. Methods: The review focused on the results achieved with the evolution of therapy following the discovery of effective chemotherapeutic agents. Results: There was an improvement in survival during the first decade following the introduction of effective chemotherapy and limb salvage replaced amputation in the majority of patients. Attempts to rescue pulmonary metastases patients with surgical intervention were also enhanced but produced only minor improvement in survival. An international collaborative study, EURAMOS has been launched to investigate the utility of neoadjuvant chemotherapeutic agents in improving survival based upon their efficacy in the treatment of the primary tumor. Conclusions: New agents and or new strategies are urgently required to improve the outcome in Osteosarcoma.
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