title: A comprehensive safety evaluation of trabectedin and drug-drug interactions of trabectedin-based combinations.
abstract: Trabectedin (Yondelis(®)) is a potent marine-derived antineoplastic drug with high activity against various soft tissue sarcoma (STS) subtypes as monotherapy, and in combination with pegylated liposomal doxorubicin (PLD) for the treatment of patients with relapsed platinum-sensitive ovarian cancer. This article reviews the safety and pharmacokinetic profiles of trabectedin. Records were identified using predefined search criteria using electronic databases (e.g. PubMed, Cochrane Library Database of Systematic Reviews). Primary peer-reviewed articles published between 1 January 2006 and 1 April 2014 were included. The current safety and tolerability profile of trabectedin, based on the evaluation in clinical trials of patients treated with the recommended treatment regimens for STS and recurrent ovarian cancer, was reviewed. Trabectedin as monotherapy or in combination with PLD, was not associated with cumulative and/or irreversible toxicities, such as cardiac, pulmonary, renal, or oto-toxicities, often observed with other common chemotherapeutic agents. The most common adverse drug reactions (ADRs) were myelosuppression and transient hepatic transaminase increases that were usually not clinically relevant. However, trabectedin administration should be avoided in patients with severe hepatic impairment. Serious and fatal ADRs were likely to be related to pre-existing conditions. Doxorubicin or PLD, carboplatin, gemcitabine, or paclitaxel when administered before trabectedin, did not seem to influence its pharmacokinetics. Cytochrome P450 (CYP) 3A4 has an important role in the metabolism of trabectedin, suggesting a risk of drug-drug interactions with trabectedin used in combination with other CYP3A4 substrates. Trabectedin has a favorable risk/efficacy profile, even during extended treatment in pretreated patients.
authors.affiliation: Science of Health Department, School of Medicine, University "Magna Graecia" of Catanzaro, Viale Europa-Germaneto, 88100, Catanzaro, Italy.
authors.forename: Christian
authors.initials: C
authors.lastname: Leporini
authors.forename: Marinella
authors.initials: M
authors.lastname: Patanè
authors.forename: Francesca
authors.initials: F
authors.lastname: Saullo
authors.forename: Pierandrea
authors.initials: P
authors.lastname: Rende
authors.forename: Luca
authors.initials: L
authors.lastname: Gallelli
authors.forename: Eugenio Donato
authors.initials: ED
authors.lastname: Di Paola
authors.forename: Rosa
authors.initials: R
authors.lastname: Toscano
authors.forename: Maria
authors.initials: M
authors.lastname: Lucia
authors.forename: Marco
authors.initials: M
authors.lastname: Rossi
authors.forename: Giovambattista
authors.initials: G
authors.lastname: De Sarro
authors.forename: Emilio
authors.initials: E
authors.lastname: Russo
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use*; D004149:Dioxoles / Q000008:administration & dosage / Q000009:adverse effects*; D004347:Drug Interactions / Q000528:radiation effects; D005260:Female; D006801:Humans; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D012509:Sarcoma / Q000188:drug therapy*; D044005:Tetrahydroisoquinolines / Q000008:administration & dosage / Q000009:adverse effects*; D000077606:Trabectedin
chemical_list: D000970:Antineoplastic Agents; D004149:Dioxoles; D044005:Tetrahydroisoquinolines; D000077606:Trabectedin