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

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 G(2)-M phase. In the clinical setting, after failure of! standard treatment, ET-743 at 15 mg/m(2) 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 1 2 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 Ill 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.