Trabectedin and its potential in the treatment of soft tissue sarcoma

Abstract

Philippe A Cassier1, Armelle Dufresne1, Jean-Yves Blay1,2,3, Jérôme Fayette2,31Unité de Jour d’Oncologie Médicale Multidisciplinaire, Hôpital Edouard Herriot, Lyon, France; 2Département d’Oncologie Médicale, Centre Léon Bérard, Lyon, France; 3Unité INSERM 590, Equipe Cytokine et Cancer, Centre Léon Bérard, Lyon, FranceAbstract: 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 µg/m² 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: chemotherapy, sarcoma, drug development, DNA repair