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3.1. Trabectedin in Soft Tissue Sarcoma The efficacy of trabectedin as salvage chemotherapy in adults with advanced, recurrent STS was assessed in three nonrandomized phase II trials [53, 54, 56] and in chemotherapy-na?ve patients with unresectable advanced STS of multiple histologies [55]. A phase II randomized registration ET-743-STS-201 study (ClinicalTrials.gov Identifier: NCT00060944) in 270 patients with advanced liposarcoma (n = 93, 34.4%) and leiomyosarcoma (n = 177, 65.6%; 30 patients, 17% with U-LMS) after failure of prior conventional chemotherapy demonstrated a superior disease control of trabectedin 1.5?mg/m2 given as a 24-hour i.v. infusion q3w compared with a weekly trabectedin regimen (0.58?mg/m2; 3-hour i.v. infusion for three see more consecutive weeks in a 4-week cycle) in terms of longer time to progression (median TTP: 3.7 versus 2.3 months; p = 0.0302), median PFS (3.3 versus 2.3 months; p = 0.0418), and median OS (13.9 versus 11.8 months; p = 0.1920) [57]. These benefits from trabectedin therapy in patients treated MLN8237 concentration using a 24?h infusion q3w were highlighted by PFS rate at 3 months (51.5%) and 6 months (35.5%), which surpassed the thresholds criteria established by the EORTC to define drug activity in pretreated STS [82]. Based on these results, in 2007, trabectedin was the first anticancer marine-derived drug to be approved in the European Union and in many other countries worldwide for the treatment of adult patients with advanced STS after failure of anthracyclines and ifosfamide or for those patients who are unsuitable to receive these agents [105]. Although the response rate to trabectedin in pretreated patients with STS is rather low (Aldosterone administration of trabectedin appears to be associated with improved efficacy outcomes when compared with short-term and later treatments [52, 53, 106]. Recent evidence have demonstrated that trabectedin, in addition to direct growth inhibition, has additional immunomodulatory effects, which exerts significant effects on the tumor microenvironment (see above) that may help to explain this phenomenon which commonly becomes apparent after several cycles of treatment. Thus, any decision to stop treatment with trabectedin should always be carefully evaluated by the clinician. Treatment duration with trabectedin as an important factor for long-term outcomes was reported in the French expanded access program [107].