The Role of Chemotherapy in the Treatment of Bone and Soft-tissue Sarcomas

Abstract

OverviewSarcomas are rare, mesenchymal tumors of the soft tissue and bone that exhibit a marked heterogeneity in their clinical presentation, biologic behavior, and histologic features. Approximately 10,400 new cases are diagnosed annually, 7800 of which arise from the soft tissues (50–60% of which involve the extremities) and 2600 from bones.1 Although the incidence of extremity sarcomas is similar to that of Hodgkin’s disease, they are responsible for more than twice as many deaths each year. Major advances in the treatment of these tumors have been limited by an inability to accumulate sufficient numbers of similar patients to perform prospective randomized clinical trials with results that can achieve statistical significance.Until the 1970s, surgery and/or radiation therapy was the accepted method for the primary management of most soft-tissue and bone sarcomas of the extremities. However, surgery alone, especially wide resection, was associated with a high incidence of local recurrences. Even when local control was achieved, more than 50% of patients with soft-tissue sarcoma and 80% of patients with skeletal sarcoma (osteogenic and Ewing’s sarcoma) eventually developed distant metastases and died, usually within 2 years.2–11 Systemic chemotherapy was subsequently found to exhibit reproducible anti-tumor effects against these neoplasms. Initially used only in the treatment of metastatic disease, this was later used as a part of combined-modality therapy in the adjuvant (postoperative) setting, and then as preoperative (neoadjuvant, induction) therapy in an attempt to preserve limb function and/or increase long-term survival.2–11 The routes of chemotherapy administration have included intravenous (IV) bolus, continuous IV infusion, and local (regional) drug delivery directly to the tumor via a feeding artery.12