Advances in neoadjuvant chemotherapy in soft tissue sarcomas.

The use of adjuvant chemotherapy in soft tissue sarcomas (STS) continues to be an area of controversy; however, the group of investigators favoring the use of an anthracycline- and ifosfamide-based regimen for high-risk (American Joint Committee on Cancer stage III) extremity STS is steadily increasing. The historic 5-year survival rate of approximately 50% in this high-risk group treated with local therapy alone represents a poor standard of care, thus there is a need to incorporate systemic therapy early in the management of these patients. Published data from the meta-analysis of doxorubicin-based adjuvant chemotherapy trials and the prospective randomized data with epirubicin and ifosfamide from the Italian Sarcoma Group are frequently used as rationale for this approach. In a rare and heterogenous group of diseases, such as STS, physicians run into negative studies for various reasons that have little to do with the efficacy of the treatment being tested. The wisdom may be in capitalizing further on a positive lead as opposed to nihilism. It is appropriate to acknowledge that the chemotherapeutic agents have limited efficacy and are toxic, especially when used at full therapeutic doses. Selecting patients in whom there is some evidence of benefit, justifying the poor quality of life from receiving chemotherapy, becomes very important. This rationale, with the lessons learned from osteosarcoma research, forms the basis for neoadjuvant chemotherapy for STS. Until we reach the day when we have identified critical tumorigenic targets and their effective inhibitors for most of these tumors, we are obligated to use the available therapeutic armamentarium in the best possible sequence.