Eisen, Tim and Shparyk, Yaroslav and Macleod, Nicholas and Jones, Robert and Wallenstein, Gudrun and Temple, Graham and Khder, Yasser and Dallinger, Claudia and Studeny, Matus and Loembe, Arsene-Bienvenu and Bondarenko, Igor (2013) 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. Investigational New Drugs, Vol.31 (Iss 5). pp. 1283-1293. ISSN 0167-6997 (Print) 1573-0646 (Online)
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Abstract
PURPOSE: 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 end point) 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. CONCLUSION: Nintedanib administered at 200 mg twice daily was not associated with clinically relevant QT prolongation.
| Item Type: | Article |
|---|---|
| Additional Information: | doi: 10.1007/s10637-013-9962-7 |
| Uncontrolled Keywords: | Nintedanib, BIBF 1120, Renal cell carcinoma, RCC, QT interval, Phase II, Angiogenesis inhibitor. |
| Subjects: | Pharmacology Oncology |
| Divisions: | Departments > Department of Oncology and Medical Radiology |
| Depositing User: | Елена Шрамко |
| Date Deposited: | 04 Apr 2017 12:20 |
| Last Modified: | 04 Apr 2017 12:37 |
| URI: | http://repo.dma.dp.ua/id/eprint/1577 |
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