Abstract
Thirty to 50% of patients with adult type soft tissue sarcoma will develop metastasis. At this stage, systemic chemotherapy is then generally proposed when a complete resection of all metastasis is not feasible (Clark et al. 2005). The two most active therapeutic drugs for advanced soft tissue sarcomas are doxorubicin and ifosfamide; dacarbazine although considered as the third active agent, actually shows a marginal activity. Initial response rates to doxorubicin single agent regimens are 10–30% with 5–8% long term survivors (Blay et al. 2003, 2004). The combination of doxorubicin with ifosfamide has yielded higher response rate (25–70%), but with no survival improvement. After failure of doxorubicin and ifosfamide, few therapeutic options are available. The combination of gemcitabine and docetaxel was reported to induce high response rates and progression free survival (PFS) in leiomyosarcomas (Bay et al. 2006). ET-743, trabectedin, Yondelis®, is a tetrahydro-isoquinoline alkaloid isolated from Ectenascidia turbinata, a tunicate that grows on mangrove roots throughout the Caribbean sea. ET-743 interferes with the activity of several transcription factors and traps protein from the nucleotide excision repair (NER) system, thus resulting in DNA damage, modulation of expression of various genes, and blockade of cells in G2-M phase. After failure of doxorubicin and/or ifosfamide, as well as in first line treatment, ET-743 at 1.5 mg/m2 in 24 h CI every 21 days yielded an overall response rate close to 8% and 30–40% stabilisation rates. Leiomyosarcomas, liposarcomas (in particular myxoid 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. In vitro, ET-743 exerts synergistic cytotoxic activity with doxorubicin or cisplatin, and in vivo with irinotecan. Phase I combination studies are in currently progress. We detail all these aspects of ET-743.
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Fayette, J. et al. (2010). Sarcoma: Treatment with Ecteinascidin-743. In: Hayat, M. (eds) Methods of Cancer Diagnosis, Therapy, and Prognosis. Methods of Cancer Diagnosis, Therapy and Prognosis, vol 6. Springer, Dordrecht. https://doi.org/10.1007/978-90-481-2918-8_35
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