New developments in treatment of ovarian carcinoma: focus on trabectedin

Philippe A Cassier1, Aude Duret1*, Olivier Trédan1, Nicolas Carrabin2, Pierre Méeus2, Isabelle Treilleux3, Jean-Paul Guastalla1, Isabelle Ray-Coquard1,41Département de médecine, 2Département de chirurgie, and 3Département d’anatomopathologie, Centre Léon Bérard, 4EA 4129 SIS Lyon, France *DeceasedAbstract: 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, and ovarian and breast cancer, and combination with various other chemotherapeutic drugs seems feasible. Toxicities are mainly hematologic 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. The recently reported results of a large Phase III trial comparing pegylated liposomal doxorubicin (PLD) alone with a combination of PLD and trabectedin in patients with recurrent ovarian cancer showed improved progression-free survival with the combination of trabectedin and PLD, albeit at the price of increased toxicity. Current research focuses on the identification of predictive factors for patients treated with trabectedin, as well as the development of other combinations.Keywords: chemotherapy, ovarian cancer, combination, drug development, DNA repair