Soft Tissue Sarcoma Knowledge Centre
Management
Chemotherapy
While both surgery and radiotherapy aim to achieve local control of the tumour, chemotherapy aims to achieve systemic control and thus has a potential role in the management of patients with metastatic disease1.
The drugs with proven efficacy against STS are doxorubicin, ifosfamide, dacarbazine (DTIC), trabectedin, and the combination of gemcitabine and docetaxel, the latter not being approved indications according to EMEA or FDA. Most multidrugs regimens contain either doxorubicin used as a single agent (A) at an optimal dose of 75 mg/m2, or a combination of doxorubicin and ifosfamide (AI) possibly associated with dacarbazine (MAID), the most recently reported combination being gemcitabine and docetaxel, which yielded a survival advantage in a recently reported trial in 2007. Higher response rates are obtained with combined chemotherapy regimens, but phase III comparative studies have demonstrated no survival benefit of the combination of drugs over single-agent doxorubicin. Four types of approaches are used in patients with STS.
Adjuvant chemotherapy
About 15 randomised phase III trials have evaluated the benefit of postoperative adjuvant chemotherapy to prevent local relapse in high-risk STS patients with localised disease. Because STS is a rare disease, most trials have involved relatively small patient populations. In a majority of cases, a reduction of the risk of local recurrence has been observed among patients receiving adjuvant chemotherapy. Some other studies have shown a lower risk of metastatic progression, whereas only few have reported improved survival under treatment. Ameta-analysis of all published studies has confirmed a significant reduction of the risk of relapse, either local or metastatic, but with a non-significant reduction of the risk of death. The recent EORTC 62931 trial, reported in American Society of Clinical Oncology 2007, failed to demonstrate any survival benefit nor reduction in the risk of relapse. In consequence, adjuvant chemotherapy cannot be considered a standard option for patients with STS, and treatment must be tailored to the needs of each individual patient. The most commonly used regimens are combinations of doxorubicin and ifosfamide (AI or MAID).
Neoadjuvant chemotherapy
Neoadjuvant chemotherapy is used prior to surgery to control microscopic residual disease and shrink the size of the tumour in order to allow complete, oncologically effective surgical resection (R0, or at least R1). This strategy is used for the treatment of “locally advanced” tumours.
Reference:
1. Clark MA, Fisher C et al. (2005) “Soft-tissue sarcomas in adults.” N Engl JMed 353(7): 701–11