Clinical impact of trabectedin (ecteinascidin-743) in advanced/metastatic soft tissue sarcoma.
BACKGROUND
Patients with advanced or metastatic non-gastrointestinal stromal tumour soft tissue sarcoma (STS) whose disease progresses during or after chemotherapy with doxorubicin or ifosfamide have few options and very limited life expectancy. In this setting, the DNA and transcription interacting agent trabectedin (ecteinascidin-743), isolated originally from the tunicate Ecteinascidia turbinata, has encouraging activity and is now approved in the European Union.


OBJECTIVE
To review evidence for the efficacy of trabectedin in STSs.


METHODS
This review includes material known to the authors through preclinical and clinical work with trabectedin, and information from relevant papers and abstracts.


RESULTS
Pooled analysis of Phase II studies suggests that around 50% of STS patients, failing conventional chemotherapy, experienced long lasting tumour control (either objective response or stabilization of disease) when treated with trabectedin. Twenty-nine per cent of patients were alive at 2 years, and median overall survival was 10.3 months. Leiomyosarcomas and liposarcomas appear particularly sensitive to the drug. In myxoid and round-cell liposarcomas trabectedin seems exceptionally active. A link between specific translocations underlying this disease and the drug's mechanism of action is being explored. Trabectedin is also active in synovial, ewing sarcoma and other translocation-related STSs. Trabectedin is not cardio- or neurotoxic. The neutropenia and hepatic toxicity that occur are non-cumulative, reversible, and lessened by steroid premedication. The lack of cumulative toxicities could make trabectedin appropriate for prolonged treatment.


CONCLUSIONS
The potential of trabectedin should be further explored in STSs in general and in specific subtypes, both in combination with other cytotoxic agents and with modulators of intracellular signalling.
Catholic University Leuven, University Hospital Gasthuisberg, Department of General Medical Oncology, Leuven Cancer Institute, Herestraat 49, 3000 Leuven, Belgium. patrick.schoffski@uz.kuleuven.be
Patrick
P
Schöffski
Herlinde
H
Dumez
Pascal
P
Wolter
Cristiana
C
Stefan
Agnieszka
A
Wozniak
Jose
J
Jimeno
Allan T
AT
Van Oosterom
D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D004149:Dioxoles / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D018572:Disease-Free Survival; D006801:Humans; D015394:Molecular Structure; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D012509:Sarcoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D044005:Tetrahydroisoquinolines / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D000077606:Trabectedin
D018906:Antineoplastic Agents, Alkylating; D004149:Dioxoles; D044005:Tetrahydroisoquinolines; D000077606:Trabectedin