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Trabectedin for advanced soft tissue sarcomas: optimizing use

Authors Reid A, Martin-Liberal J, Benson C

Received 12 July 2014

Accepted for publication 30 September 2014

Published 12 December 2014 Volume 2014:10 Pages 1003—1011


Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 3

Editor who approved publication: Professor Garry Walsh

Alison Reid, Juan Martin-Liberal, Charlotte Benson

Sarcoma Unit, The Royal Marsden NHS Foundation Trust, London, UK

Abstract: Patients with locally advanced or metastatic soft tissue sarcoma have a poor outlook with median survival in the order of 1 year. There is therefore an urgent need for novel agents to impact this disease. Trabectedin is one such novel agent that has demonstrated activity for patients with advanced soft tissue sarcoma and it was licensed in Europe in 2007 for patients in the second-line setting or first-line in those patients deemed unsuitable to receive cytotoxics. In order to best serve patients with novel agents, it is imperative to understand the mechanism or mechanisms of action and the best ways of assessing response in order to optimize antitumor activity. Frequently, the mechanism of action and the optimal means of assessing response will be different from those of traditional cytotoxics. Trial design should reflect these factors to ensure that active drugs are not wrongly marked as futile. This review discusses a number of factors that may influence the optimization of trabectedin use. These factors include the administration schedule, the optimal timing of trabectedin administration in the disease process, the histopathological and molecular subtypes that may be most sensitive to trabectedin, the challenge of assessing response, particularly using radiology, and, finally, the safety considerations with this agent.

Keywords: trabectedin, soft tissue sarcomas, ET-743, myxoid lipoarcomas, optimal administration

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