According to these preliminary results, the gemcitabine/docetaxel combination might be of interest in sarcoma, but randomised phase III studies are required to confirm whether or not this combination deserves a place in the management of advanced pretreated STS patients [Sleijfer 2008, Bay 2007]. Due to disappointing results in the phase II trials, in the last 30 years, no drugs had been approved in Europe or in the United States for the treatment of patients with STS (except for GIST).

There was, therefore, a clear need for effective salvage treatments, particularly for patients with advanced STS and for whom both doxorubicin and ifosfamide, administered either consecutively as first- and second-line therapy or in combination as first-line therapy, have failed [Hartmann 2005]..

Yondelis® has been demonstrated to provide clinical benefit in many patients in whom STS progresses despite current anthracycline and ifosfamide therapy. Following demonstration of promising activity in preclinical and phase I studies in solid tumours, the clinical activity of Yondelis® was investigated in single-arm phase II studies in patients with STS [García-Carbonero 2004; Le Cesne 2005; Yovine 2004], and clinical benefit has subsequently been

demonstrated in a large, randomised phase II clinical trial in patients with liposarcoma and leiomyosarcoma [Demetri 2009]. The results of these studies have shown that Yondelis® arrests tumour growth in approximately 50% of patients and produces statistically significant prolongation of the time to tumour progression (TTP), as well as PFS, in patients with STS after failure of at least both anthracyclines and ifosfamide [García-Carbonero 2004; Le Cesne 2005; Demetri 2009; Yovine 2004]. Yondelis® response rate, toxicity profile and pharmacokinetics were also evaluated as first-line therapy in patients with unresectable advanced soft tissue sarcoma (STS) in a multicenter Phase II study with 36 patients. The recommended regimen (1.5 mg/m² every 3 weeks over 24-hours infusion) resulted in durable disease control rates with an ORR of 17.1%, median duration of response of 16.1 months, PFS rates exceeding 20% at 6 and 12 months and an OS rate of 72% at 1 year. A complete response was observed in one patient with myxoid liposarcoma [García Carbonero 2005, Blay 2009]. In addition, the safety profile of Yondelis® has been well characterised and Yondelis® treatment has been found to be generally well tolerated [Demetri 2009].