Trabectedin: safety and efficacy in the treatment of advanced sarcoma

Abstract

Soft tissue sarcomas (STS) are a rare group of malignancies with multiple different subtypes. Close to half of intermediate or high grade STS develop metastatic disease. Treatment of recurrent/metastatic sarcomas is quite challenging with only a few drugs showing measurable benefits. Trabectedin (ecteinascidin 743, ET-743, Yondelis) is a newly developed alkylating agent that has shown significant broad spectrum potential as a single agent second line drug alone or in combination particularly in the treatment of liposarcomas and leiomyosarcomas. Clinical benefit rates seem to favor its use especially in pretreated patients with recurrent/metastatic disease. The drug is well tolerated in general but hepatotoxicity and hematologic side effects are common. Approved in Europe, the currently ongoing Phase III trials along with the already existing clinical evidence may provide enough data for the Food and Drug Administration for an approval in the US.

Keywords: efficacy; leiomyosarcoma; liposarcoma; metastatic sarcoma; side effects; trabectedin.

Figure 1.

Structure of trabectedin: (1′R,6R,6aR,7R,13S,14S,16R)-6′,8, 14-trihydroxy-7′,9-dimethoxy-4,10,23-trimethyl-19-oxo-3′, 4′,6,7,12,13,14,16-octahydrospiro[6,16-epithiopropanooxymethano)-7,13-imino-6aH-1,3-dioxolo[7,8]isoquino[3,2-b][3]benzazocine-20,1′(2′H)-isoquinolin]-5-yl acetate.