Osteosarcoma is the most common malignant primary bone
tumor in children and adolescents. Current optimal treatment for
osteosarcoma consists of multi-agent
chemotherapy and aggressive surgical resection of all sites of disease involvement. The current national and international cooperative trial for patients with newly diagnosed
osteosarcoma builds upon the backbone of
cisplatin,
doxorubicin, and
methotrexate. This protocol is designed to clarify whether (i) the addition of
ifosfamide and
etoposide to postoperative
chemotherapy with
cisplatin,
doxorubicin, and
methotrexate improves the event-free survival and overall survival for patients with resectable
osteosarcoma and a poor histologic response to 10 weeks of preoperative
chemotherapy; and (ii) the addition of pegylated interferon-alpha-2b as maintenance
therapy after postoperative
chemotherapy with
cisplatin,
doxorubicin, and
methotrexate improves the event-free survival and overall survival for patients with resectable
osteosarcoma and a good histologic response to 10 weeks of preoperative
chemotherapy. However, the optimal treatment strategy (or strategies) for patients with relapsed or metastatic disease has yet to be defined. This remains one of the persistent challenges in the treatment of
osteosarcoma. Recent therapeutic advances have focused on circumventing
chemotherapy resistance mechanisms, incorporation of non-classical agents into upfront
therapy, targeting of the
tumor micro-environment, and investigating the role of novel delivery mechanisms. In patients with localized disease the 5-year survival rate is at least 70%; patients with metastatic or recurrent disease have <20% chance of long-term survival despite aggressive
therapies. These figures have changed little in the past 2 decades. This review focuses on the current
therapy for
osteosarcoma, and highlights emerging strategies that will hopefully change the outlook for patients with this disease.