title: The efficacy of trabectedin in treating ovarian cancer.
abstract: The majority of women with epithelial ovarian cancer present with advanced stage disease and there is a critical need for novel drugs and treatment strategies to improve outcomes. Trabectedin is a unique cytotoxic agent with a complex mechanism of action. It binds to guanines in the N2 position in the minor groove of DNA and its cytotoxicity involves DNA repair pathways and transcription regulation. Trabectedin's activity is also related to the drug-induced changes of the tumor microenvironment. It has been shown to improve progression-free survival in combination with pegylated liposomal doxorubicin in patients with platinum-sensitive relapsed ovarian cancer. The most common adverse events experienced with trabectedin are nausea, vomiting, fatigue, neutropenia and transaminitis. Studies of biomarkers that are predictors of trabectedin benefit are underway. Areas covered: This review covers trabectedin's mechanism of action and pharmacology, the clinical development of the drug in ovarian cancer, ongoing trials, and the use of biomarkers to predict efficacy to trabectedin. Expert opinion: Ongoing phase III trials with biomarker studies will help to elucidate the patient population that will best benefit from trabectedin and pave the way for personalized treatment decisions and potential future approval of trabectedin in the United States.
authors.affiliation: a Don Monti Division of Hematology & Medical Oncology , Hofstra Northwell School of Medicine, Monter Cancer Center , Lake Success , NY , USA.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Teplinsky
authors.affiliation: b Paul & Carolyn Flory Endowed Professor , University of Cincinnati Cancer Institute , Cincinnati , OH , USA.|c Department of Obstetrics and Gynecology , University of Cincinnati , Cincinnati , OH , USA.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Herzog
mesh_terms: D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry / Q000627:therapeutic use*; D000077216:Carcinoma, Ovarian Epithelial; D017326:Clinical Trials, Phase III as Topic; D004149:Dioxoles / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry / Q000627:therapeutic use*; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D055808:Drug Discovery; D005260:Female; D006801:Humans; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000473:pathology; D009375:Neoplasms, Glandular and Epithelial / Q000188:drug therapy* / Q000473:pathology; D009503:Neutropenia / Q000139:chemically induced; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D044005:Tetrahydroisoquinolines / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry / Q000627:therapeutic use*; D000077606:Trabectedin; D059016:Tumor Microenvironment / Q000187:drug effects
chemical_list: D018906:Antineoplastic Agents, Alkylating; D004149:Dioxoles; D044005:Tetrahydroisoquinolines; C506643:liposomal doxorubicin; D011092:Polyethylene Glycols; D004317:Doxorubicin; D000077606:Trabectedin
keywords: BRCA; DNA repair pathways; Trabectedin; ovarian cancer; pegylated liposomal doxorubicin; platinum-resistant; platinum-sensitive; recurrent ovarian cancer