Abstract
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.
Highlights
In the current era long term survival in Osteosarcoma is achieved in approximately 66% of patients with localized extremity primaries and 25% - 30% of patients with axial primaries or patients presenting with pulmonary metastases [1]
During the last three decades, treatment has stagnated with permutations and combinations of the few available effective agents: doxorubicin (DOX), highdose methotrexate with leucovorin “rescue” (MTX), cisdiaminedichloroplatium II (Cisplatin, [CDP]) and ifosfamide (IFX) or Cyclophosphamide (CTX)
Some basic questions require further investigation. These include, but are not limited to, which “standard” chemotherapeutic agents alone or in combination could produce an optimal result; will alterations in the postoperative regimen improve the poor prognosis of patients with an initial unfavorable histological tumor response to neoadjuvant chemotherapy (NACT-see later) and the role of immunomodulation? This communication will provide a demarche of the principal chemotherapeutic agents in current use in the treatment of osteosarcoma
Summary
In the current era long term survival in Osteosarcoma is achieved in approximately 66% of patients with localized extremity primaries and 25% - 30% of patients with axial primaries or patients presenting with pulmonary metastases [1]. During the last three decades, treatment has stagnated with permutations and combinations of the few available effective agents: doxorubicin (DOX), highdose methotrexate with leucovorin “rescue” (MTX), cisdiaminedichloroplatium II (Cisplatin, [CDP]) and ifosfamide (IFX) or Cyclophosphamide (CTX). It is uncertain if these agents are used in an optimal manner. This communication will provide a demarche of the principal chemotherapeutic agents in current use in the treatment of osteosarcoma It will briefly review other agents under investigation. Prior to that the Conpadri regimen devised by Sutow, was investigated It comprised [pulsed] cyclophosphamide, vincristine (Oncovin), l-phenylalanine mustard [4]. Recent communications have demonstrated responses with Gemcitabine (GEM) [9] and Cediranib (CED) [10]
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