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Chemotherapy-induced Vascular Toxicity - Real-time In vivo Imaging of Vessel Impairment
Published on: January 7, 2015
Cardiovascular toxicities associated with vascular endothelial growth factor receptor tyrosine kinase inhibitors: a
Yao Zhang1, Junge Deng2, Jize Wang3
1The Second Clinical Medical College, Lanzhou University, Lanzhou, China.
Background:
Vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs) are widely used in the treatment of various cancers. However, post-marketing evidence regarding their cardiovascular toxicities remains limited.
Aim:
This pharmacovigilance study aimed to comprehensively evaluate the association between VEGFR-TKIs and cardiovascular toxicities in cancer patients.
Method:
We retrieved and analyzed cardiovascular toxicity reports related to VEGFR-TKIs from the FDA Adverse Event Reporting System (FAERS). Disproportionality analyses were performed using the proportional reporting ratio (PRR), reporting odds ratio (ROR), information component (IC), and empirical Bayes geometric mean (EBGM) to detect safety signals of cardiovascular toxicities associated with VEGFR-TKIs.
Results:
A total of 12,726 cancer patients experienced cardiovascular toxicities associated with VEGFR-TKI treatment. All eleven VEGFR-TKIs were associated with cardiovascular toxicities, with hypertension being the most consistently reported event across all agents. Among them, cabozantinib was associated with the highest number of cardiovascular events, whereas lenvatinib exhibited the strongest signal. Notably, lenvatinib was associated with cardiac failure (ROR = 2.521, PRR = 2.479, IC = 1.308, EBGM = 2.476) and cardiomyopathy (ROR = 2.801, PRR = 2.788, IC = 1.476, EBGM = 2.782); sunitinib with cardiac failure (ROR = 2.745, PRR = 2.693, IC = 1.426, EBGM = 2.687) and cardiomyopathy (ROR = 3.020, PRR = 3.004, IC = 1.584, EBGM = 2.997); ponatinib with cardiomyopathy (ROR = 3.393, PRR = 3.372, IC = 1.752, EBGM = 3.368); and vandetanib with Torsade de pointes/QT prolongation (ROR = 27.930, PRR = 26.101, IC = 4.703, EBGM = 26.051).
Conclusion:
VEGFR-TKIs were associated with cardiovascular toxicities, particularly hypertension. Notably, lenvatinib and sunitinib were associated with cardiac failure and cardiomyopathy, ponatinib with cardiomyopathy, and vandetanib with Torsade de pointes and QT prolongation. Future prospective studies are warranted to further clarify the causal relationships between these agents and cardiovascular toxicities.
Insights
Vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs) are linked to cardiovascular toxicities, especially hypertension. Lenvatinib, sunitinib, ponatinib, and vandetanib show specific risks like cardiac failure, cardiomyopathy, and QT prolongation.
Area of Science:
- Pharmacovigilance and Oncology
- Cardiovascular Toxicology
- Drug Safety Evaluation
Background:
- Vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs) are crucial in cancer therapy.
- Limited post-marketing data exists on the cardiovascular toxicities of VEGFR-TKIs.
Purpose of the Study:
- To conduct a pharmacovigilance study assessing the association between VEGFR-TKIs and cardiovascular toxicities in cancer patients.
- To identify specific VEGFR-TKIs and their related cardiovascular adverse events.
Main Methods:
- Utilized the FDA Adverse Event Reporting System (FAERS) for cardiovascular toxicity reports linked to VEGFR-TKIs.
- Employed disproportionality analyses, including PRR, ROR, IC, and EBGM, to detect safety signals.
Main Results:
- Identified 12,726 cancer patients with cardiovascular toxicities associated with VEGFR-TKI treatment.
- All eleven VEGFR-TKIs showed associations with cardiovascular toxicities, with hypertension being most common.
- Lenvatinib and sunitinib were linked to cardiac failure and cardiomyopathy; ponatinib to cardiomyopathy; and vandetanib to Torsade de pointes/QT prolongation.
Conclusions:
- VEGFR-TKIs are associated with significant cardiovascular toxicities, notably hypertension.
- Specific agents like lenvatinib, sunitinib, ponatinib, and vandetanib present distinct cardiovascular risks.
- Further prospective research is recommended to establish causal relationships between VEGFR-TKIs and cardiovascular adverse events.
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