Abstract
Trabectedin is a new marine-derived compound that binds the DNA minor groove and interacts with proteins of the DNA-repair machinery. Trabectedin has shown promising single-agent activity in pretreated patients with soft-tissue sarcoma (STS) and ovarian and breast cancer; combination with various other chemotherapeutic drugs is feasible. Toxicities are mainly hematological and hepatic, with grade 3-4 neutropenia and thrombocytopenia observed in approximately 50 and 20% of patients, respectively, and grade 3-4 elevation of liver transaminases observed in 35-50% of patients treated with trabectedin. Trabectedin obtained regulatory approval by the EMEA and in other countries for the treatment of STS patients after failure of all available standard-of-care chemotherapy. Current research focuses on the identification of predictive factors for patients treated with trabectedin as well as the development of other combinations.
MeSH terms
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Antineoplastic Agents, Alkylating / adverse effects
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Antineoplastic Agents, Alkylating / pharmacokinetics
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Antineoplastic Agents, Alkylating / therapeutic use*
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Breast Neoplasms / drug therapy
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Breast Neoplasms / physiopathology
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Controlled Clinical Trials as Topic
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DNA Repair / drug effects
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Dioxoles / adverse effects
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Dioxoles / pharmacokinetics
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Dioxoles / therapeutic use*
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Female
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Humans
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Liver / drug effects
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Liver / enzymology
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Neutropenia / chemically induced
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Ovarian Neoplasms / drug therapy
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Ovarian Neoplasms / physiopathology
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Sarcoma / drug therapy*
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Sarcoma / physiopathology
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Tetrahydroisoquinolines / adverse effects
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Tetrahydroisoquinolines / pharmacokinetics
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Tetrahydroisoquinolines / therapeutic use*
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Thrombocytopenia / chemically induced
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Trabectedin
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Transaminases / drug effects
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Transaminases / metabolism
Substances
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Antineoplastic Agents, Alkylating
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Dioxoles
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Tetrahydroisoquinolines
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Transaminases
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Trabectedin