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


RESULTS
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.


CONCLUSIONS
ET-743 is a novel active drug for sarcoma which yields prolonged disease-free survival in subsets of patients.
Fayette
Jérôme
J
Hôpital Edouard Herriot, Service d'oncologie médicale, France.
Coquard
Isabelle Ray
IR
Alberti
Laurent
L
Boyle
Helen
H
Méeus
Pierre
P
Decouvelaere
Anne-Valérie
AV
Thiesse
Philippe
P
Sunyach
Marie-Pierre
MP
Ranchère
Dominique
D
Blay
Jean-Yves
JY
D018906:Antineoplastic Agents, Alkylating / Q000737:chemistry / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D004247:DNA / Q000737:chemistry; D004260:DNA Repair; D004149:Dioxoles / Q000737:chemistry / Q000627:therapeutic use*; D018572:Disease-Free Survival; D006801:Humans; D008956:Models, Chemical; D009362:Neoplasm Metastasis; D012509:Sarcoma / Q000188:drug therapy*; D044005:Tetrahydroisoquinolines / Q000737:chemistry / Q000627:therapeutic use*; D000077606:Trabectedin; D016896:Treatment Outcome
D018906:Antineoplastic Agents, Alkylating; D004149:Dioxoles; D044005:Tetrahydroisoquinolines; D004247:DNA; D000077606:Trabectedin