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• W2023735727 abstract "Abstract Learning Objectives After completing this course, the reader will be able to: Describe the original mechanism of action of ET-743.Explain the management of patients treated with ET-743, including what biological exams are needed because of toxicity and what is the optimal schedule of administration.Choose the best histological subtype of sarcoma for treatment with ET-743 and describe the clinical aim of treatment.Discuss putative combinations of ET-743 with other therapies. Access and take the CME test online and receive 1 AMA PRA category 1 credit at CME.TheOncologist.com Ecteinascidin-743 (ET-743) is a natural product derived from the marine tunicate Ectenascidia turbinate. ET-743 binds in the minor groove of DNA, blocks transcription factors activity, and traps protein from the nucleotide excision repair system, thus blocking cells in G2-M phase. ET-743 demonstrated cytotoxic activity at very low concentrations against sarcoma cell lines in pre-clinical studies. In several phase II clinical studies in patients with advanced sarcoma failing conventional doxorubicin- and ifosfamide-based chemotherapy, ET-743 delivered by continuous intravenous 24-hour infusion at a dose of 1,500 μg/m2 every 21 days yielded 8% overall response and 30%–40% stabilization rates for a clinical benefit rate close to 40%. Interestingly, long-term stabilizations over more than 3 years have been described. In vivo, ET-743 has a specific toxicity profile, the major toxicity of this product being hepatic, through biliary duct destruction, and hematologic. ET-743 has also been evaluated in first-line treatment for these patients. Finally, due to its original mode of action and the lack of cross-resistance with other chemotherapy agents, ET-743 was tested in a preclinical model in combination with other drugs. Synergy was reported in vitro with doxorubicin and cisplatin; phase I combination studies are in progress." @default.
• W2023735727 created "2016-06-24" @default.
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• W2023735727 date "2005-11-01" @default.
• W2023735727 modified "2023-10-14" @default.
• W2023735727 title "ET-743: A Novel Agent with Activity in Soft Tissue Sarcomas" @default.
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• W2023735727 doi "https://doi.org/10.1634/theoncologist.10-10-827" @default.
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