ET-743: a novel agent with activity in soft-tissue sarcomas.

Abstract

PURPOSE OF REVIEW:

ET-743 (ecteinascidin-743, trabectedin, Yondelis) is a natural marine product that has shown clinical activity in sarcoma. This paper reviews the current knowledge on this compound.

RECENT FINDINGS:

ET-743 interferes with several transcription factors, traps protein from the nucleotide-excision repair system, thus resulting in DNA damage, modulates gene expression, and blocks cells in the G2-M phase. In the clinical setting, after failure of standard treatment, ET-743 at 1.5 mg/m2 in 24 h continuous infusion every 21 days yielded an overall response rate close to 8% and stabilization rates of 30-40%, some lasting beyond 3 years. Leiomyosarcomas, liposarcomas, and synovial sarcomas may be the more sensitive histotypes. The major toxicities of ET-743 are hepatic--through biliary duct destruction--and hematologic. They are not cumulative and a significant number of patients may receive 12 courses or more. In a randomized Phase II study testing weekly ET-743 with treatment every 3 weeks, an improved progression-free survival rate was observed in the 3-weekly arm; the results of the follow-up Phase III trial should be available at the American Society of Clinical Oncology meeting of 2006. Phase I combination studies are in currently progress.

SUMMARY:

ET-743 is a novel active drug for sarcoma which yields prolonged disease-free survival in subsets of patients.

• Authors: Jérôme Fayette, Isabelle Ray Coquard, Laurent Alberti, Helen Boyle, Pierre Méeus, Anne-Valérie Decouvelaere, Philippe Thiesse, Marie-Pierre Sunyach, Dominique Ranchère, Jean-Yves Blay
• Journal: Current opinion in oncology (Curr Opin Oncol) Vol. 18 Issue 4 Pg. 347-53 (Jul 2006) ISSN: 1040-8746 [Print] United States
• PMID: 16721129 (Publication Type: Journal Article, Review)

Chemical References

• Antineoplastic Agents, Alkylating
• Dioxoles
• Tetrahydroisoquinolines
• DNA
• Trabectedin

Topics

• Antineoplastic Agents, Alkylating (chemistry, therapeutic use)
• Clinical Trials as Topic
• DNA (chemistry)
• DNA Repair
• Dioxoles (chemistry, therapeutic use)
• Disease-Free Survival
• Humans
• Models, Chemical
• Neoplasm Metastasis
• Sarcoma (drug therapy)
• Tetrahydroisoquinolines (chemistry, therapeutic use)
• Trabectedin
• Treatment Outcome