Trabectedin for the treatment of soft tissue sarcomas.
BACKGROUND
Trabectedin, a marine-derived DNA-binding antineoplastic agent, has been registered by the EMA and recently also by the FDA for the treatment of patients with advanced soft-tissue sarcoma (STS), a rare and heterogeneous disease.


METHODS
The antitumor activity of trabectedin is related both to direct effects on cancer cells, such as growth inhibition, cell death and differentiation, and indirect effects related to its anti-inflammatory and anti-angiogenic properties. Furthermore, trabectedin is the first compound that targets an oncogenic transcription factor with high selectivity in mixoid liposarcomas. This peculiar mechanism of action is the basis of its clinical development. The clinical pharmacology of trabectedin, the subsequent phase I, II and III trials are summarized and put into perspectives in this review.


CONCLUSIONS
Trabectedin is a relevant pleiotropic antitumoral agent within the complex scenario of the management of STS. It can be used in advanced STS, either after failure of anthracyclines and ifosfamide or in patients unfit for these drugs, especially when reaching a high-tumor control and a long-term benefit is a priority. Toxicity profile is acceptable and manageable with no reported cumulative toxicities. Therefore, trabectedin has become one relevant therapeutic option in metastatic STS, especially in selected histologies.
a Department of Medical Oncology and Hematology , Humanitas Cancer Center IRCCS , Rozzano , Milan , Italy.|b Molecular and Cellular Networks Lab, Department of Anatomy, Histology, Forensic Medicine and Orthopaedics , "Sapienza" University , Rome , Italy.
Rita
R
De Sanctis
a Department of Medical Oncology and Hematology , Humanitas Cancer Center IRCCS , Rozzano , Milan , Italy.
Andrea
A
Marrari
a Department of Medical Oncology and Hematology , Humanitas Cancer Center IRCCS , Rozzano , Milan , Italy.|c Humanitas University , Rozzano , Milan , Italy.
Armando
A
Santoro
D000818:Animals; D018943:Anthracyclines / Q000493:pharmacokinetics / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000627:therapeutic use; D018906:Antineoplastic Agents, Alkylating / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002986:Clinical Trials as Topic / Q000379:methods; D004149:Dioxoles / Q000493:pharmacokinetics / Q000627:therapeutic use*; D019468:Disease Management; D006801:Humans; D007069:Ifosfamide / Q000493:pharmacokinetics / Q000627:therapeutic use; D012509:Sarcoma / Q000175:diagnosis* / Q000188:drug therapy* / Q000378:metabolism; D044005:Tetrahydroisoquinolines / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000077606:Trabectedin; D016896:Treatment Outcome
D018943:Anthracyclines; D000970:Antineoplastic Agents; D018906:Antineoplastic Agents, Alkylating; D004149:Dioxoles; D044005:Tetrahydroisoquinolines; D000077606:Trabectedin; D007069:Ifosfamide
ET-743; Trabectedin; soft tissue sarcoma; treatment