title: Effect of small angiokinase inhibitor nintedanib (BIBF 1120) on QT interval in patients with previously untreated, advanced renal cell cancer in an open-label, phase II study.
abstract: OBJECTIVE
  Some targeted anticancer agents are associated with serious ventricular tachyarrhythmias, which may be predicted by electrocardiographic evaluation of drug-related QT prolongation. We studied the effects of nintedanib (BIBF 1120; an oral, triple angiokinase inhibitor targeting vascular endothelial growth factor, fibroblast growth factor, and platelet-derived growth factor receptors) on the QT interval in patients with renal cell carcinoma (RCC) participating in an open-label phase II trial.
  
  
  METHODS
  Treatment-naïve, adult patients with unresectable/metastatic, clear cell RCC received nintedanib 200 mg twice daily. QT intervals were evaluated at baseline (day -1), on day 1 (after the first dose), and on day 15 (steady state) by 12-lead electrocardiograms (ECGs) performed in triplicate. Pharmacokinetic sampling was also undertaken.
  
  
  RESULTS
  Among 64 evaluable patients, the upper limits of the 2-sided 90 % confidence intervals for the adjusted mean time-matched changes in QTcF interval (corrected for heart rate by Fridericia's method) from baseline to day 1 and 15 (primary ECG endpoint) were well below the regulatory threshold of 10 ms at all times. No relationship between nintedanib exposure and change from baseline in QTcF was seen. Nintedanib was generally well tolerated with no drug-related cardiovascular adverse events.
  
  
  CONCLUSIONS
  Nintedanib administered at 200 mg twice daily was not associated with clinically relevant QT prolongation.
authors.affiliation: Cambridge University Health Partners, Addenbrooke's Hospital, Cambridge, CB2 0QQ, UK, tgqe2@cam.ac.uk.
authors.forename: Tim
authors.initials: T
authors.lastname: Eisen
authors.forename: Yaroslav
authors.initials: Y
authors.lastname: Shparyk
authors.forename: Nicholas
authors.initials: N
authors.lastname: Macleod
authors.forename: Robert
authors.initials: R
authors.lastname: Jones
authors.forename: Gudrun
authors.initials: G
authors.lastname: Wallenstein
authors.forename: Graham
authors.initials: G
authors.lastname: Temple
authors.forename: Yasser
authors.initials: Y
authors.lastname: Khder
authors.forename: Claudia
authors.initials: C
authors.lastname: Dallinger
authors.forename: Matus
authors.initials: M
authors.lastname: Studeny
authors.forename: Arsene-Bienvenu
authors.initials: AB
authors.lastname: Loembe
authors.forename: Igor
authors.initials: I
authors.lastname: Bondarenko
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000097:blood / Q000494:pharmacology* / Q000627:therapeutic use; D002292:Carcinoma, Renal Cell / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology*; D004562:Electrocardiography / Q000187:drug effects; D005260:Female; D006801:Humans; D007211:Indoles / Q000097:blood / Q000494:pharmacology* / Q000627:therapeutic use; D007680:Kidney Neoplasms / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D047428:Protein Kinase Inhibitors / Q000097:blood / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D007211:Indoles; D047428:Protein Kinase Inhibitors; C530716:nintedanib