Published in:
01-10-2015 | Original Article
A phase I open-label trial evaluating the cardiovascular safety of regorafenib in patients with advanced cancer
Published in: Cancer Chemotherapy and Pharmacology | Issue 4/2015
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Purpose
To characterize the cardiovascular safety profile of regorafenib in patients with advanced cancer.
Methods
Patients received regorafenib 160 mg/day for 21 days followed by a 7-day break. The primary endpoint was the change from baseline in QTcF at the regorafenib t
max (Day 21, Cycle 1 or 2) and changes in left ventricular ejection fraction (LVEF) from baseline on Cycle 2, Day 21. Secondary objectives were pharmacokinetics, safety, anti-tumor activity and effects on electrocardiogram intervals. QT intervals were corrected using the methods of Fridericia (QTcF) and Bazett (QTcB). LVEF was assessed by multigated acquisition scanning.
Results
Fifty-three patients were enrolled, and all received at least one dose of regorafenib 160 mg. Twenty-five patients received regorafenib for 21 days without dose reduction. The mean change from baseline in QTcF at t
max was (−)2 ms (90 % CI −8, 3). No patient experienced a change from baseline in QTcF > 60 ms, and two had QTcF changes between 30 and 60 ms. No patient had a QTcF or QTcB > 480 ms. In 27 patients who received at least 80 mg of regorafenib, the mean change from baseline in LVEF% ± SD was 1.7 ± 7.8. In 14 patients without a dose reduction, the mean change from baseline in LVEF% was (−)0.1 ± 8.6 at Cycle 2, Day 21. Four patients experienced a LVEF decrease between 10 and 20 %.
Conclusion
The effects of regorafenib on the QT/QTc interval and LVEF were modest and unlikely to be of clinical significance in the setting of advanced cancer therapy.