Trabectedin

Abstract

After completing this course, the reader will be able to:1. Enumerate the clinical indications for trabectedin therapy.2. Describe the mechanism of action and the pharmacokinetics of trabectedin.3. Analyze the toxicity profile and appraise the therapeutic effects associated with trabectedin.This article is available for continuing medical education credit at CME.TheOncologist.com. CME CME INTRODUCTIONTrabectedin (ET-743, Yondelis; Ortho Biotech Products, Horsham, PA) is a natural product that was originally isolated from the Caribbean sea squirt, Ecteinascidia turbinata but is now manufactured through an entirely synthetic route (Fig. 1) [1]. Trabectedin is a highly potent alkylator, and its cytotoxicity is thought to be mediated through a novel interaction with DNA repair pathways.

A retrospective pooled analysis of trabectedin safety in 1,132 patients with solid tumors treated in phase II clinical trials

“…In addition, the exclusion of patients with known active liver disease and close monitoring during treatment provided adequate opportunity to deny, adjust, delay or discontinue treatment using established guidelines [24,38]. Notably, the incidence of bilirubin and alkaline phosphatase elevations was very low and neither was cumulative.…”

Prospects and challenges for the development of new therapies for Ewing sarcoma

“…ET-743 is a natural product isolated from the sea squirt Ecteinascidia turbinate. The drug has been extensively studied in phase I and II studies in sarcomas in both the United States and Europe and found to have activity in leiomyosarcoma, liposarcoma, malignant fibrous histiocytoma, and synovial sarcoma (Chuk et al, 2009;Thornton, 2010). However, the most impressive response rates have occurred in myxoid liposarcoma where an almost 50% response rate has been observed in some series (Grosso et al, 2009;Cesne et al, 2012).…”

Bioanalytical Aspects of Clinical Mass Balance Studies in Oncology

“…Moreover, particularly in oncology, high-potency agents have been developed, which are administered in only a few milligrams. Examples are the marinederived product trabectedin (recommended dose of 1.5 mg/m 2 ) [6] and the marine sponge product analogue eribulin (recommended dose of 1.4 mg/m 2 ) [104]. The extended collection times as well as the low doses pose challenges to the sensitivity of the quantitative assays [7,8].…”