, Volume 70, Issue 3, pp 355-376
Date: 17 Sep 2012


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Trabectedin (Yondelis®) is a tetrahydroisoquinoline molecule that was originally derived from a marine organism. It is indicated in the EU and many other countries for use in patients with advanced soft-tissue sarcoma (STS) who have progressed despite receiving previous treatment with anthracyclines and ifosfa-mide or in those who are unable to receive these agents. It is also approved in the EU in combination with pegylated liposomal doxorubicin for the treatment of platinum-sensitive, recurrent ovarian cancer. In addition, trabectedin holds orphan drug status for the treatment of advanced, recurrent STS in the US, Switzerland and Korea, and for the treatment of advanced, recurrent ovarian cancer in the US and Switzerland.

Clinical trials showed that intravenous trabectedin was effective in chemotherapy-experienced patients with advanced, recurrent liposarcoma or leiomyosarcoma, and results from a retrospective analysis suggest that the drug may be particularly effective in patients with advanced myxoid liposarcoma. In addition, coadministration of trabectedin with pegylated liposomal doxorubicin was associated with a significantly longer progression-free survival (6 weeks) than pegylated liposomal doxorubicin monotherapy in patients with recurrent ovarian cancer after failure of first-line, platinum-based chemotherapy. The tolerability profile of trabectedin was manageable in clinical trials, and the tolerability profile of concomitant trabectedin and pegylated liposomal doxorubicin was generally consistent with that of each agent alone. Results to date indicate that trabectedin is a valuable addition to the group of second-line antineoplastic agents available for the treatment of advanced, recurrent STS, and that it is a beneficial treatment for recurrent ovarian cancer after failure of first-line, platinum-based chemotherapy when administered in conjunction with pegylated liposomal doxorubicin.

Various sections of the manuscript reviewed by: F. Grosso, Adult Sarcoma Medical Treatment Unit, IRCCS Foundation-National Cancer Institute, Milan, Italy; M. Hensley, Gynecologic Medical Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York, USA; P. Hohenberger, Division of Surgical Oncology and Thoracic Surgery, Mannheim University Medical Center, Mannheim, Germany; R.L. Jones, Sarcoma Unit, The Royal Marsden Hospital, London, UK; B.J. Monk, Irvine Medical Center, University of California, Orange, California, USA; S.M. Schuetze, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA.

Data Selection

Sources: Medical literature published in any language since 1980 on ‘trabectedin’, identified using MEDLINE and EMBASE, supplemented by AdisBase (a proprietary database). Additional references were identified from the reference lists of published articles. Bibliographical information, including contributory unpublished data, was also requested from the company developing the drug.
Search strategy: MEDLINE, EMBASE and AdisBase search terms were ‘trabectedin’ or ‘ecteinascidin-743’ or ‘ET-743’ and ‘ovarian cancer’ or ‘ovarian neoplasms’ or ‘ovary cancer’ or ‘soft tissue sarcoma’ or ‘sarcoma’. Searches were last updated 19 January 2010.
Selection: Studies in patients with soft tissue sarcoma or ovarian cancer who received trabectedin. Inclusion of studies was based mainly on the methods section of the trials. When available, large, well controlled trials with appropriate statistical methodology were preferred. Relevant pharmacodynamic and pharmacokinetic data are also included.
Index terms: Trabectedin, soft tissue sarcoma, ovarian cancer, pharmacodynamics, pharmacokinetics, therapeutic use, tolerability.