Trial reportCancer chemotherapy and pharmacology2013
A randomized, double-blind, placebo-controlled study to evaluate the effect of repeated oral doses of pazopanib on cardiac conduction in patients with solid tumors.
Trial report in Cancer chemotherapy and pharmacology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00861029 (A Randomized, Blinded Placebo-Controlled Study to Evaluate the Effect of Repeat Oral Doses of Pazopanib), which is not on this map. Cited by 15 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Randomized, Blinded Placebo-Controlled Study to Evaluate the Effect of Repeat Oral Doses of Pazopanib (GW786034) on the Electrocardiogram (ECG) With Focus on Cardiac Repolarization (QTc Duration) in Subjects With Solid Tumors
Who cites it
15 citing papers in PubMed, 2 syntheses or guidelines pooled it, 42 citations in OpenAlex.
- Incidence, Diagnosis, and Management of QT Prolongation Induced by Cancer Therapies: A Systematic Review.Journal of the American Heart Association · 2017Pooled it
- QTc interval prolongation with vascular endothelial growth factor receptor tyrosine kinase inhibitors.British journal of cancer · 2015Pooled it
- Preparation and Characterization of Pazopanib Hydrochloride-Loaded Four-Component Self-Nanoemulsifying Drug Delivery Systems Preconcentrate for Enhanced Solubility and Dissolution.Pharmaceutics · 2022Article
- Mitochondrial Determinants of Anti-Cancer Drug-Induced Cardiotoxicity.Biomedicines · 2022Review
- c-Kit deficiency impairs nitric oxide signaling in smooth muscle cells.Biochemical and biophysical research communications · 2019Article
- The Impact of Pazopanib on the Cardiovascular System.Journal of cardiovascular pharmacology and therapeutics · 2018Review
- Pazopanib for renal cell carcinoma leads to elevated mean arterial pressures in a murine model.Clinical and experimental hypertension (New York, N.Y. : 1993) · 2018Article
- Clinical Pharmacokinetics and Pharmacodynamics of Pazopanib: Towards Optimized Dosing.Clinical pharmacokinetics · 2017Review
- Assessment of pazopanib-related hypertension, cardiac dysfunction and identification of clinical risk factors for their development.Cardio-oncology (London, England) · 2017Article
- Pazopanib in Patients with Clear-Cell Renal Cell Carcinoma: Seeking the Right Patient.Frontiers in pharmacology · 2017Article
- [Side effect management of tyrosine kinase inhibitors in urology : Gastrointestinal side effects].Der Urologe. Ausg. A · 2016Article
- In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib.Pharmacology research & perspectives · 2015Article
- Incidence and relevance of QTc-interval prolongation caused by tyrosine kinase inhibitors.British journal of cancer · 2015Article
- Prevention of Pazopanib-Induced Prolonged Cardiac Repolarization and Proarrhythmic Effects.Arquivos brasileiros de cardiologia · 2014Article
- The contribution of VEGF signalling to fostamatinib-induced blood pressure elevation.British journal of pharmacology · 2014Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 10 institutions in 1 country.
Funding
Abstract
purposeAs tyrosine kinase inhibitors have been associated with cardiotoxicity, we evaluated the effect of pazopanib, an inhibitor of vascular endothelial growth factor receptor, platelet-derived growth factor receptor, and c-Kit, on electrocardiographic parameters in patients with cancer.
methodsThis double-blind, placebo-controlled, parallel-group study randomized patients (N = 96) to moxifloxacin (positive control) or placebo on Day 1 followed by pazopanib or placebo 800 mg/day (fasted) on Days 2-8 and 1,600 mg (with food) on Day 9. Treatment effects were evaluated by baseline-adjusted, time-matched, serial Holter electrocardiograms.
resultsSixty-five patients were evaluable for preplanned analyses. On Day 1, the maximum mean difference in baseline-adjusted, time-matched Fridericia-corrected QT (QTcF) interval in moxifloxacin-treated patients versus placebo was 10.6 ms (90% confidence interval [CI]: 4.2, 17.0). The administration scheme increased plasma pazopanib concentrations approximately 1.3- to 1.4-fold versus the recommended 800 mg once-daily dose. Pazopanib caused clinically significant increases from baseline in blood pressure, an anticipated class effect, and an unexpected reduction in heart rate from baseline that correlated with pazopanib exposure. On Day 9, the maximum mean difference in baseline-adjusted, time-matched QTcF interval in pazopanib-treated patients versus placebo was 4.4 ms (90% CI: -2.4, 11.2). Mixed-effects modeling indicated no significant concentration-dependent effect of pazopanib or its metabolites on QTcF interval.
conclusionsPazopanib as administered in this study achieved supratherapeutic concentrations, produced a concentration-dependent decrease in heart rate, and caused a small, concentration-independent prolongation of the QTcF interval.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.