Soft Tissue Sarcoma and its Management
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 disease [Clark 2005]. Standard chemotherapy is based on anthracyclines as first line treatment. There is no formal demonstration that multi-agent chemotherapy is superior to single-agent chemotherapy with doxorubicin alone. However, a higher response rate may be expected, in particular in a number of sensitive histological types, according to several, although not all, randomised clinical trials. Therefore, multi-agent chemotherapy with doxorubicin plus ifosfamide may be the treatment of choice, especially when a tumour response is felt to be able to give an advantage and the performance status is good. Dacarbazine may be added to the regimen [Casali 2009]. Doxorubicin has been reported to induce response rates of approximately 20% (first-line), while ifosfamide response rates appeared slightly higher (19–28%) [Seynaeve 1999]. Similar response rates have been reported for epirubicin, first-line (18–29%) [Seynaeve 1999].
However, three more recent larger studies have reported response rates of only approximately 10% for doxorubicin and ifosfamide. Thus, Lorigan et al [Lorigan 2007] reported a response rate of 11.8% for doxorubicin and 5.5% and 8.4% for two regimens of ifosfamide in a phase III study involving 326 patients with advanced or metastatic STS, while van Oosterom [van Oosterom 2002] reported response rates of 10% and 25% for two different ifosfamide regimens given as first-line therapy in a phase II study, and Judson et al [Judson 2001] reported a response rate of 9% for doxorubicin and 10% for pegylated liposomal doxorubicin in a phase II study involving 94 patients.
Combination therapy with doxorubicin and ifosfamide has been shown to increase the response rate over doxorubicin alone but has not been found to improve median survival, which is approximately 12 months [Nielsen 2003]. In addition, use of doxorubicin and ifosfamide is limited by serious toxicities and frequent development of tumour resistance [Cvetkovic 2002, Bramwell 2003].