Clinical impact of trabectedin (ecteinascidin-743) in advanced/metastatic soft tissue sarcoma.

Abstract

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.

CONCLUSION:

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.

• Authors: Patrick Schöffski, Herlinde Dumez, Pascal Wolter, Cristiana Stefan, Agnieszka Wozniak, Jose Jimeno, Allan T Van Oosterom
• Journal: Expert opinion on pharmacotherapy (Expert Opin Pharmacother) Vol. 9 Issue 9 Pg. 1609-18 (Jun 2008) ISSN: 1744-7666 [Electronic] England
• PMID: 18518789 (Publication Type: Journal Article, Review)

Chemical References

• Antineoplastic Agents, Alkylating
• Dioxoles
• Tetrahydroisoquinolines
• Trabectedin

Topics

• Animals
• Antineoplastic Agents, Alkylating (administration & dosage, adverse effects, pharmacokinetics, therapeutic use)
• Clinical Trials as Topic
• Dioxoles (administration & dosage, adverse effects, pharmacokinetics, therapeutic use)
• Disease-Free Survival
• Humans
• Molecular Structure
• Neoplasm Invasiveness
• Neoplasm Metastasis
• Sarcoma (drug therapy, mortality, pathology)
• Tetrahydroisoquinolines (administration & dosage, adverse effects, pharmacokinetics, therapeutic use)
• Trabectedin