New developments in targeted therapy for soft tissue sarcoma

Soft tissue sarcomas (STS) are rare diseases, with an estimated 10,390 new cases in the United States in 2008. Unfortunately, only 50% are cured with surgical resection. The standard cytotoxic chemotherapeutic agents have not been successful in the treatment of metastatic disease. The standard single-agent chemotherapy for metastatic disease is doxorubicin, with only 20% to 25% response rates. The combination of doxorubicin with other agents, such as ifosfamide, has improved response rates, without any improvement in overall survival. New targeted therapies have shown some activity in STS; however, disease stabilization is seen more often than a true radiographic response. The combination of cytotoxic chemotherapy with more targeted and novel agents may be appropriate to improve outcome in these patients. The agents of interest in sarcomas at this time are multi-tyrosine kinase inhibitors, antiangiogenesis agents, inhibitors of mammalian target of rapamycin, hypoxia-activating prodrugs, insulin growth factor monoclonal antibodies, and tumor necrosis factor-related apoptosis-inducing ligand agonists.