title: Trabectedin has a low cardiac risk profile: a comprehensive cardiac safety analysis.
abstract: OBJECTIVE
  This analysis provides a cross-study evaluation of the cardiac safety of trabectedin.
  
  
  METHODS
  Drug-related cardiac adverse events (CAEs) were retrieved from phase I-III clinical trials, pharmacovigilance databases, and spontaneously reported cases. Left ventricular ejection fraction (LVEF) was monitored in combination phase I studies with doxorubicin or pegylated liposomal doxorubicin (PLD) and in a phase III trial (with PLD).
  
  
  RESULTS
  CAEs [grade 4 cardiac arrest with severe pancytopenia and sepsis (n = 1 patient), grade 4 atrial fibrillation (n = 2), and grade 1 tachycardia (n = 1)] occurred in 4/283 patients (1.4%) in 6 single-agent phase I trials. CAEs (grade 1 sinus tachycardia in a hypertensive patient and grade 1 ventricular dysfunction) occurred in 2/155 patients (1.3%) in 4 phase I combination trials. Results from 19 single-agent phase II trials showed CAEs in 20/1,132 patients (1.8%): arrhythmias (tachycardia/palpitations; n = 13; 1.1%) were the most common. A rather similar rate of symptomatic CAEs was observed in both arms of a phase III trial in recurrent ovarian cancer: 6/330 patients (1.8%; PLD) and 11/333 patients (3.3%; trabectedin/PLD). No clinically relevant LVEF changes occurred in phase I combination trials. In the phase III trial, LVEF decreases from baseline were similar: 9% of patients (PLD) and 7% (trabectedin/PLD), with no relevant symptoms. During postmarketing experience in soft tissue sarcoma (2,046 patients treated), 4 CAEs (2 cardiac arrest, 2 cardiac failure; ~0.2%) occurred in patients with preexisting conditions.
  
  
  CONCLUSIONS
  Trabectedin has a low incidence of CAEs, consisting mainly of arrhythmias. This extensive data review indicates a low cardiac risk profile for trabectedin.
authors.affiliation: PharmaMar, Colmenar Viejo, Madrid, Spain.
authors.forename: Claudia
authors.initials: C
authors.lastname: Lebedinsky
authors.forename: Javier
authors.initials: J
authors.lastname: Gómez
authors.forename: Youn C
authors.initials: YC
authors.lastname: Park
authors.forename: Antonio
authors.initials: A
authors.lastname: Nieto
authors.forename: Arturo
authors.initials: A
authors.lastname: Soto-Matos
authors.forename: Trilok
authors.initials: T
authors.lastname: Parekh
authors.forename: Vicente
authors.initials: V
authors.lastname: Alfaro
authors.forename: Elena
authors.initials: E
authors.lastname: Roy
authors.forename: Pilar
authors.initials: P
authors.lastname: Lardelli
authors.forename: Carmen
authors.initials: C
authors.lastname: Kahatt
mesh_terms: D018906:Antineoplastic Agents, Alkylating / Q000009:adverse effects* / Q000627:therapeutic use; D004149:Dioxoles / Q000009:adverse effects* / Q000627:therapeutic use; D006321:Heart / Q000187:drug effects*; D006801:Humans; D018570:Risk Assessment; D044005:Tetrahydroisoquinolines / Q000009:adverse effects* / Q000627:therapeutic use; D000077606:Trabectedin
chemical_list: D018906:Antineoplastic Agents, Alkylating; D004149:Dioxoles; D044005:Tetrahydroisoquinolines; D000077606:Trabectedin