Trabectedin therapy for sarcomas

PURPOSE OF REVIEW: The therapeutic armamentarium of adult soft-tissue sarcomas (STS) has widened in recent years. This was also due to increased consideration of their variegated histology. Trabectedin is a new chemotherapeutic agent, which significantly strengthens the armamentarium along this direction. RECENT FINDINGS: Trabectedin has proven efficacy in STS, mainly in leiomyosarcomas, liposarcomas, and other translocation-related sarcomas. Among further subgroups, its activity in uterine leiomyosarcomas is noteworthy. Moreover, it exerts special antitumor activity in myxoid liposarcomas, with distinct patterns of tumor response. Also, its mechanism of action is distinct in myxoid liposarcoma, apparently overcoming lipogenic cell differentiation block due to the tumor chromosomal translocation. Apart from histology, DNA repair mechanisms have been investigated as a predictive factor, with retrospective evidence in support. Combination of trabectedin with doxorubicin has limitations due to additive toxicity. Trabectedin is well tolerated as a single agent. Occasional major myelosuppression is possible but proper patient selection (with a focus on liver tests) and possibly steroid premedication are of help. SUMMARY: Trabectedin is a new marine-derived drug with a definite role in the 'histology-driven' medical therapy of STS. There is room for further investigation, to fully elucidate its efficacy in all STS and optimize tolerability.