Home
Resources
Publications
Electrocardiographic Characterization of the QTc Interval in Patients With Advanced Solid Tumors: Pharmacokinetic- Pharmacodynamic Evaluation of Sunitinib

Electrocardiographic Characterization of the QTc Interval in Patients With Advanced Solid Tumors: Pharmacokinetic- Pharmacodynamic Evaluation of Sunitinib

Carlo L Bello, Marilyn Mulay, Xin Huang, Shem Patyna, Melissa Dinolfo, Steven Levine, Andrew Van Vugt, Melvin Toh, Charles Baum, Lee Rosen

Clin Cancer Res. 2009 Nov 15;15(22):7045-52.

PMID: 19903787

Abstract:

Purpose:
To evaluate the effects of sunitinib, a multitargeted tyrosine kinase inhibitor, on the QT interval in patients with cancer.
Experimental design:
Patients received sunitinib loading doses (150-200 mg) on days 3 and 9 and maintenance doses (50 mg/d) on days 4 to 8. Moxifloxacin (day 1), placebo (day 2), and granisetron [with placebo (day 2) or sunitinib (days 3 and 9)] were also administered. Treatment effects were evaluated by time-matched, serial electrocardiograms, and manually overread.
Results:
Twenty-four of 48 patients were QT/PK evaluable. Moxifloxacin produced a time-matched, maximum mean placebo-adjusted corrected QT interval (QT(c)F) of 5.6 ms [90% confidence interval (CI), 1.9-9.3]. Sunitinib QT(c)F changes correlated with exposure, but not T(max). Maximum mean time-matched, placebo-adjusted QT(c)F was 9.6 ms (90% CI, 4.1-15.1) at steady state/therapeutic concentrations (day 3) and 15.4 ms (90% CI, 8.4-22.4) at supratherapeutic concentrations (day 9). No patient had a QT(c)F >500 ms. Concomitant granisetron produced no significant QT(c)F prolongation. Sunitinib-related adverse events were as previously described.
Conclusions:
Sunitinib has a dose-dependent effect on QT interval. The increased risk of ventricular arrhythmias must be weighed against the therapeutic benefit sunitinib provides to patients with advanced cancer.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP141136018	Granisetron Related Compound C		141136-01-8	Price

As a specialist in analytical chemical Products, Alfa Chemistry offers consumers a wealth of raw materials and a full range of technologies and services.

QUICK LINKS

HEADQUARTERS

Tel:

Fax:

Email: