Salvage therapy for soft tissue sarcomas

The clinical management of sarcomas, tumors of the connective tissue, is complicated by their relative rarity and pathologic heterogeneity. Adequate first-line treatment is essential to diminish the need for salvage therapy, and includes diagnostic incisional biopsy, appropriate staging of disease extent locally and systemically, and, at resection, careful assessment of surgical margins and tumor grade and size. In patients with resectable limb-sparing disease, local control is most frequently achieved with surgery and preoperative or postoperative radiotherapy. In patients with isolated pulmonary recurrence, pulmonary metastatectomy is clearly indicated. For soft tissue sarcomas, chemotherapy is palliative. Only two drugs, doxorubicin (and its analogue, epirubicin) and ifosfamide, have demonstrated more than 20% activity in soft tissue sarcomas. The two leading combination regimens currently are cyclophosphamide/doxorubicin/dacarbazine (CyADIC) and mesna/doxorubicin/ifosfamide with or without dacarbazine (MAI +/- D), which, when used aggressively, achieve response rates of 40% to 57%. In metastatic disease, however, there appears to be no survival advantage to using combination chemotherapy over single agents used in sequence. Biologic agents, including tumor necrosis factor and gamma interferon, have not been effective as single agents, but antiangiogenic therapy with alpha interferon may have synergy when combined with chemotherapy. Clearly, new chemotherapeutic agents and agents to overcome drug resistance mechanisms are needed to bolster the efficacy of therapy for patients with sarcomas.