QTc interval prolongation with vascular endothelial growth factor receptor tyrosine kinase inhibitors

Ghatalia, Pooja; Je, Youjin; Kaymakcalan, Marina D.; Sonpavde, Guru; Choueiri, Toni K.

doi:10.1038/bjc.2014.564

Cited by 123 publications

(90 citation statements)

References 46 publications

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“…4.4% of patients treated with TKIs developed all grade QTc prolongation and 0.8% developed serious arrhythmia (99). However, the incidence of QT prolongation is not affected by the duration of therapy (99).…”

Section: Qt Prolongationmentioning

confidence: 99%

See 1 more Smart Citation

Cardiovascular Complications of Cancer Therapy

Chang

Okwuosa

Scarabelli

et al. 2017

Journal of the American College of Cardiology

237

105

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In this second part of a 2-part review, we will review cancer or cancer-therapy associated systemic and pulmonary hypertension, QT-prolongation, arrhythmias, pericardial disease, and radiation-induced cardiotoxicity. This review is based on MEDLINE literature search, published clinical guidelines, and best practices in major cancer centers. Newly developed targeted therapy can exert off-target effects causing hypertension, thromboembolism, QT-prolongation and atrial fibrillation. Radiation therapy often accelerates atherosclerosis. Furthermore, radiation can damage the heart valves, the conduction system, and pericardium that may take years to manifest clinically. Management of pericardial disease in cancer patients also posed clinical challenges. This review highlights the unique opportunity of caring for cancer patients with heart problems caused by cancer or cancer therapy. It is an invitation to action for cardiologists to become familiar with this emerging subspecialty.

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Section: Qt Prolongationmentioning

confidence: 99%

“…However, the incidence of QT prolongation is not affected by the duration of therapy (99). The most common drugs that prolongs QTc when used in conjunction with sunitinib are domperidone or loperamide (104); nonetheless, there were no high-grade arrhythmias or sudden cardiac deaths associated with sunitinib use.…”

Section: Qt Prolongationmentioning

confidence: 99%

Cardiovascular Complications of Cancer Therapy

Chang

Okwuosa

Scarabelli

et al. 2017

Journal of the American College of Cardiology

237

105

View full text Add to dashboard Cite

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“…It is noteworthy that hypertension caused by tyrosine kinases inhibitors is associated with several fatal complications, such as left ventricular ejection fraction (LVEF) dysfunction, cardiac failure and coronary artery disease [37][38][39]. Previous reports analysed the incidence of cardiac events in patients treated with sorafenib and consequently revealed that 33.8% experienced a cardiac event with typical symptoms or with changes in ECG and biochemical indicators (CK-MB, TNT) [37].…”

Section: Cardiovascular Eventsmentioning

confidence: 99%

The Adverse Effects of Sorafenib in Patients with Advanced Cancers

Gao

2015

Basic Clin Pharma Tox

131

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Sorafenib is the first multi-kinase inhibitor (TKI) approved for the treatment of advanced hepatocellular cancer (HCC) and metastatic renal cell cancer (RCC) and is increasingly being used to treat patients with well-differentiated radioiodine-resistant thyroid cancer (DTC). Sorafenib demonstrates targeted activity on several families of receptor and non-receptor tyrosine kinases that are involved in angiogenesis, tumour growth and metastatic progression of cancer. Sorafenib treatment results in longterm efficacy and low incidence of life-threatening toxicities. Although sorafenib has demonstrated many benefits in patients, the adverse effects cannot be ignored. The most common treatment-related toxicities include diarrhoea, fatigue, hand-foot skin reaction and hypertension. Most of these toxicities are considered mild to moderate and manageable to varying degrees; however, cardiovascular events might lead to death. In this MiniReview, we summarize the adverse effects of sorafenib that commonly occur in patients with advanced cancers.Over the past few years, targeted therapy utilizing multi-tyrosine kinase inhibitors (TKIs) has been widely used for treatment of cancers. TKIs are designed to block specific cancer cell processes and are usually better tolerated than most conventional chemotherapeutic drugs. Sorafenib is the first orally active TKI approved by the Food and Drug Administration (FDA). Sorafenib mainly targets vascular endothelial growth factor (VEGFR1-3) and Raf kinases. Other reported targets include K-Ras, BRAF, V599E mutant BRAF, platelet-derived growth factor receptor-b (PDGFR-b), FMS-like tyrosine kinase 3 (FLT3), c-Kit and RET, and several other receptor tyrosine kinases (RTKs) via various modes of action, such as inhibition of the Ras/Raf/MAPK and PI3K/AKT/mTOR signalling pathways [1][2][3]. The anticancer activity of sorafenib thus results from a dual inhibitory effect towards angiogenesis and tumour cell proliferation. Sorafenib also possesses the function of inducing apoptosis in cancer cells by inhibiting the phosphorylation of initiation factor eIF4E and loss of the antiapoptotic protein myeloid cell leukaemia-1(Mcl-1) [4].In 2007, sorafenib was approved by the FDA for the treatment of advanced hepatocellular cancer (HCC) [5,6] and metastatic renal cell cancer (RCC) [7,8]. Oral administration of sorafenib is associated with improved quality of life and prolonged overall survival of patients [9]. Recently, the most positive phase III results were observed in well-differentiated radioiodine-resistant thyroid cancer (DTC) [10], resulting in the increased use of sorafenib to treat patients with DTC.

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“…Additionally, a randomized, doubleblind, placebo-controlled trial of repeated oral doses of pazopanib in patients with solid tumors revealed a concentration-dependent decrease in heart rate and a small concentration-independent prolongation of the QTcF interval [14]. A recent trial-level meta-analysis of 6548 patients treated within randomized phase II and III trials comparing arms with and without a FDA-approved VEGFR TKI reported that these can be associated with QTc prolongation albeit of low clinical significance [15]. Notably, regorafenib was not included in this analysis because QTc prolongation was not listed as an adverse event in any of the trials.…”

Section: Discussionmentioning

confidence: 99%