Trabectedin is a new marine-derived compound that binds the DNA minor groove and interacts with proteins of the DNA repair machinery. Phase I trials have established the standard regimen as 1500 mug/m(2) 24-hour continuous infusion repeated every 3 weeks. Several phase II trials have shown response in 5%-10% of unselected patients with soft tissue sarcoma failing prior chemotherapy and disease stabilisation in 30%-40%. Furthermore, prolonged disease control has been described in 15%-20% of patients. Toxicities are mainly haematological 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 enzymes observed in 35%-50% of patients treated with trabectedin. Current research focuses on the identification of predictive factors for patients with soft tissue sarcoma treated with trabectedin.
Keywords: DNA repair; chemotherapy; drug development; sarcoma.