title: Effect of trabectedin on the QT interval in patients with advanced solid tumor malignancies.
abstract: OBJECTIVE
  The primary objective of this study was to access the potential effects of trabectedin on the QT/QTc interval in patients with locally advanced or metastatic solid tumors.
  
  
  METHODS
  Patients (n = 75) who had received ≤3 previous lines of chemotherapy and had either relapsed or had progressive disease were enrolled. Patients were administered 3-h intravenous infusions of placebo (saline) on day 1 and trabectedin (1.3 mg/m(2)) on day 2. Time-matched serial triplicate ECG recordings and pharmacokinetic blood samples were collected over 24 h on both days. Heart rate corrected mean QT intervals and changes from predose baseline in QTc (ΔQTc) were assessed. The difference in ΔQTc between trabectedin and placebo was calculated at each time point (ΔΔQTc).
  
  
  RESULTS
  The upper limits of the 90% confidence interval for ΔΔQTcF and ΔΔQTcB at all time points were less than the prespecified noninferiority margin of 10 ms (≤6.65 ms). No patient had a QTc > 500 ms or a time-matched increase from baseline in QTc > 60 ms at any time point. Regression analyses indicated ΔΔQTc was poorly correlated with trabectedin concentration. No adverse events suggestive of proarrhythmic potential were reported.
  
  
  CONCLUSIONS
  Trabectedin did not prolong the QTc interval. Safety and pharmacokinetic profiles of trabectedin were similar to that observed in other ovarian and breast cancer studies.
authors: Cancer Centers of North Carolina-Asheville, 20 Medical Park Drive, Asheville, NC 28803, USA. raymond.thertulien@usoncology.com
authors: R
authors: R
authors: Thertulien
authors: G M
authors: GM
authors: Manikhas
authors: L Y
authors: LY
authors: Dirix
authors: J B
authors: JB
authors: Vermorken
authors: K
authors: K
authors: Park
authors: M M
authors: MM
authors: Jain
authors: J J
authors: JJ
authors: Jiao
authors: J
authors: J
authors: Natarajan
authors: T
authors: T
authors: Parekh
authors: P
authors: P
authors: Zannikos
authors: A P
authors: AP
authors: Staddon
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D001247:Asthenia / Q000139:chemically induced; D004149:Dioxoles / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004562:Electrocardiography / Q000187:drug effects; D005260:Female; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D016037:Single-Blind Method; D044005:Tetrahydroisoquinolines / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000077606:Trabectedin; D016896:Treatment Outcome; D014839:Vomiting / Q000139:chemically induced; D055815:Young Adult
chemical_list: D018906:Antineoplastic Agents, Alkylating; D004149:Dioxoles; D044005:Tetrahydroisoquinolines; D000077606:Trabectedin