Unveiled: Why diglyceride May Make Us All Happier

The markedly reduced production of proinflammatory mediators, such as CCL2, interleukin-6 (IL-6), and the proangiogenic VEGF, may underlie the strong association between chronic inflammation and cancer progression [98�C101]. Taken together, trabectedin is more than a cytotoxic drug given that it also has immunomodulatory and antiangiogenic properties which potentially contribute to a delayed response with a prolonged stabilization [102]. Consequently, the characteristic late and long-lasting responses reported with trabectedin have now gained greater theoretical support from the perspective of considering trabectedin diglyceride as a multitarget drug with far more multifaceted activity than originally formulated [103, 104]. This is an active area of research both in preclinical and translational settings. 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 selleckchem 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 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 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 find more 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 (