Dataset Information

Effect of trabectedin on the QT interval in patients with advanced solid tumor malignancies.

ABSTRACT:

Purpose

The primary objective of this study was to access the potential effects of trabectedin on the QT/QTc interval in patients with locally advanced or metastatic solid tumors.

Methods

Patients (n = 75) who had received ?3 previous lines of chemotherapy and had either relapsed or had progressive disease were enrolled. Patients were administered 3-h intravenous infusions of placebo (saline) on day 1 and trabectedin (1.3 mg/m(2)) on day 2. Time-matched serial triplicate ECG recordings and pharmacokinetic blood samples were collected over 24 h on both days. Heart rate corrected mean QT intervals and changes from predose baseline in QTc (?QTc) were assessed. The difference in ?QTc between trabectedin and placebo was calculated at each time point (??QTc).

Results

The upper limits of the 90% confidence interval for ??QTcF and ??QTcB at all time points were less than the prespecified noninferiority margin of 10 ms (?6.65 ms). No patient had a QTc > 500 ms or a time-matched increase from baseline in QTc > 60 ms at any time point. Regression analyses indicated ??QTc was poorly correlated with trabectedin concentration. No adverse events suggestive of proarrhythmic potential were reported.

Conclusion

Trabectedin did not prolong the QTc interval. Safety and pharmacokinetic profiles of trabectedin were similar to that observed in other ovarian and breast cancer studies.

SUBMITTER: Thertulien R

PROVIDER: S-EPMC3265736 | biostudies-literature | 2012 Feb

REPOSITORIES: biostudies-literature

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Publications

Effect of trabectedin on the QT interval in patients with advanced solid tumor malignancies.

Thertulien R R Manikhas G M GM Dirix L Y LY Vermorken J B JB Park K K Jain M M MM Jiao J J JJ Natarajan J J Parekh T T Zannikos P P Staddon A P AP

Cancer chemotherapy and pharmacology 20110708 2

<h4>Purpose</h4>The primary objective of this study was to access the potential effects of trabectedin on the QT/QTc interval in patients with locally advanced or metastatic solid tumors.<h4>Methods</h4>Patients (n = 75) who had received ≤3 previous lines of chemotherapy and had either relapsed or had progressive disease were enrolled. Patients were administered 3-h intravenous infusions of placebo (saline) on day 1 and trabectedin (1.3 mg/m(2)) on day 2. Time-matched serial triplicate ECG recor ...[more]

PMID: 21739119

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Dataset Information

Effect of trabectedin on the QT interval in patients with advanced solid tumor malignancies.

Purpose

Methods

Results

Conclusion

Publications

Effect of trabectedin on the QT interval in patients with advanced solid tumor malignancies.

Similar Datasets

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