Systemic therapy of soft tissue sarcoma: an improvement in outcome.

Systemic therapy for the majority of patients with soft tissue sarcoma who require treatment of advanced unresectable or metastatic disease remains very unsatisfactory. Ifosfamide and doxorubicin remain the only agents in routine use. Treatment is usually given with palliative intent, and single-agent doxorubicin is generally regarded as the drug of choice. Inevitably, there have been efforts to determine whether or not treatment intensification yields any significant benefit. A prospective randomised trial was performed by the European Organisation for Research and Treatment of Cancer (EORTC) Soft Tissue and Bone Sarcoma Group (STBSG), which compared single-agent doxorubicin with a combination of doxorubicin and ifosfamide and also the four-drug CYVADIC (cyclophosphamide/vincristine/doxorubicin/dacarbazine) combination. There was no improvement in progression-free or overall survival associated with combination therapies, although they were significantly more toxic [1]. Subsequent attempts were made to intensify treatment by increasing the dose of doxorubicin in combination with ifosfamide, but although the results of a phase II study were promising [2], no benefit was seen in a randomised trial compared with the standard doses [3]. More recently it has been shown that ifosfamide has a more clearly defined dose– response relationship, with 9 g/m fractionated over 3 days being definitely superior to 5 g/m given as a 24-h infusion [4]. This brings into question previous combination regimens, which could be deemed suboptimal in terms of ifosfamide dose.