What is the role of QTc prolongation assessment in new drugs development phase I oncology trials

2006 Background: QT interval prolongation associated with “torsades de pointes” (TdP) has been a common cause of withdrawal from the market for several promising drugs. We determined the degree of QT prolongation in patients treated within a phase I study with a thioxanthone derivative known to have arrhythmogenic potential. Methods: Clinical data and serial ECGs from 31 patients with advanced tumors who received 86 courses of investigational drug were prospectively reviewed. The drug has been administered intravenously over 24 hours every 3 weeks. Patients have been on a 24 hour Holter monitor until 24 hours after infusion was complete. Three baseline ECGs were done and compared to those every 6 hours during therapy and once 6 hours after the infusion was complete. ECGs were read at a central lab according to a standard protocol. All QT measurements were then corrected for heart rate (QTc) using Bazett’s formula (QTc = QT interval divided by the square root of the R-R interval). Results: Overall,843 ECG ...