Yondelis® (trabectedin, ET-743): the development of an anticancer agent of marine origin
2003; Lippincott Williams & Wilkins; Volume: 14; Issue: 7 Linguagem: Inglês
10.1097/00001813-200308000-00001
ISSN1473-5741
AutoresCh. van Kesteren, M. M. M. de Vooght, Luis López Lázaro, Ron A. A. Mathôt, Jan H.M. Schellens, José Jimeno, Jos H. Beijnen,
Tópico(s)Microbial Natural Products and Biosynthesis
ResumoYondelis® (trabectedin, ET-743) is a novel antitumor agent derived from a marine source, the Caribbean tunicate Ecteinascidia turbinata. Preclinical studies demonstrated activity at low concentrations against a variety of tumors. The mechanism by which ET-743 exerts its antitumor activity has not been completely elucidated yet. Binding to the minor groove of DNA which causes a bend towards the major groove has been demonstrated. Furthermore, ET-743 interferes with DNA binding proteins and transcription factors. Clinical studies have been initiated as phase I dose-finding studies at four different treatment regimens. Dose-limiting toxicities were hematological, including neutropenia and thrombocytopenia. Furthermore, significant liver toxicity was observed, especially as a rise in transaminase levels. Antitumor activity in phase I and phase II trials was studied in multiple tumor types, including soft tissue sarcomas, melanomas and breast cancer. ET-743 is currently being extensively investigated in advanced soft tissue sarcomas. The present review describes the development of ET-743, highlighting chemical properties, mode of action, metabolism and preclinical and clinical studies.
Referência(s)