The Impact of Pazopanib on the Cardiovascular System

Justice, Cody N.; Derbala, Mohamed H.; Baich, Tesla M.; Kempton, Amber; Guo, Aaron; Ho, Thai H.; Smith, Sakima A.

doi:10.1177/1074248418769612

Cited by 25 publications

(16 citation statements)

References 121 publications

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“…Also, as an early indication of systolic dysfunction, the change in the left ventricle strain may indicate early signs of pazopanib-induced cardiotoxicity. [31][32][33] When HF develops, pazopanib should be stopped immediately, and it should be managed with standard HF therapies regardless of their cancer status as stated at The American College of Cardiology/American Heart Association guidelines. 34 Nonetheless, in the case of grades 1-2 cardiotoxicities, pazopanib could be continued at the current dose or restarted at a lower dose after treating the cardiotoxicity.…”

Section: Discussionmentioning

confidence: 99%

Pazopanib-induced fatal heart failure in a patient with unresectable soft tissue sarcoma and review of literature

Karaağaç

Eryılmaz

2019

J Oncol Pharm Pract

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Introduction Pazopanib, an oral multi-targeted tyrosine kinase inhibitor, is associated with improved outcomes in patients with unresectable or metastatic soft tissue sarcoma. Pazopanib may cause cardiotoxicity such as heart failure. Case report A 50-year-old female patient with no cardiovascular risk factors other than the previous treatment with adriamycin had a baseline left ventricular ejection fraction of 60%. She was receiving pazopanib 800 mg once daily for advanced leiomyosarcoma of the presacral area. On the 60th day of treatment, she presented with fatigue, palpitation, and exertional dyspnea for several days. Echocardiography was performed, and left ventricular ejection fraction was measured as 25%. Pazopanib-induced heart failure was considered and all other possible preliminary diagnoses were excluded. Management and outcome Pazopanib was stopped immediately. Bisoprolol fumarate 5 mg orally once daily, spironolactone 100 mg orally once daily, furosemide 40 mg orally once daily, and ramipril 2.5 mg orally once daily were started. The patient’s symptoms partially improved. Second echocardiography was performed after 15 days, and left ventricular ejection fraction was measured as 35%. But, despite pazopanib was not resumed and cardiac support treatment was administered, she died four weeks after discontinuation of pazopanib due to heart failure. Discussion Pazopanib-induced heart failure may be fatal. Physicians and patients should be aware of the cardiotoxicity risk when managing the use of pazopanib in soft tissue sarcoma.

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Section: Discussionmentioning

confidence: 99%

Pazopanib-induced fatal heart failure in a patient with unresectable soft tissue sarcoma and review of literature

Karaağaç

Eryılmaz

2019

J Oncol Pharm Pract

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“…Its clinical efficacy is also limited by the related potential cardiovascular toxicity. The clinical use of pazopanib has been associated with the development of hypertension, QT interval prolongation and other cardiovascular events triggered by oxidative stress which in turn mediates apoptosis of cardiomyocytes [ 69 ]. Ponatinib is a third-generation TKI currently approved for the treatment of chronic myeloid leukemia (CML) in patients having gatekeeper mutation T315I and that are resistant to the first and second generation TKIs.…”

Section: Oncologic Treatment Related Cardiotoxicity: the Role Of Omentioning

confidence: 99%

Molecules and Mechanisms to Overcome Oxidative Stress Inducing Cardiovascular Disease in Cancer Patients

Sabbatino

Conti

Liguori

et al. 2021

Life

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Reactive oxygen species (ROS) are molecules involved in signal transduction pathways with both beneficial and detrimental effects on human cells. ROS are generated by many cellular processes including mitochondrial respiration, metabolism and enzymatic activities. In physiological conditions, ROS levels are well-balanced by antioxidative detoxification systems. In contrast, in pathological conditions such as cardiovascular, neurological and cancer diseases, ROS production exceeds the antioxidative detoxification capacity of cells, leading to cellular damages and death. In this review, we will first describe the biology and mechanisms of ROS mediated oxidative stress in cardiovascular disease. Second, we will review the role of oxidative stress mediated by oncological treatments in inducing cardiovascular disease. Lastly, we will discuss the strategies that potentially counteract the oxidative stress in order to fight the onset and progression of cardiovascular disease, including that induced by oncological treatments.

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“…Pazopanib may be responsible for apoptosis of endothelial cells, which promotes coagulation, thus leading to thromboembolic and ischemic events in treated patients. Moreover, its inhibition of VEGF signaling may also increase blood viscosity through overproduction of erythropoietin, exacerbating risk for thrombosis, but ATEs (miocardial infarction/ischemia, cerebrovascular events) are uncommon with pazopanib (<2%) in clinical practice (32). To date, no specific data are available about ATEs risk with other VEFG inhibitors as cabozantinib, vandetanib or nintebanib.…”

Section: Drug-related Arterial Thrombosismentioning

confidence: 99%

Arterial Thrombosis in Cancer: Spotlight on the Neglected Vessels

et al. 2019

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Cancer patients are at risk for both venous and arterial thrombotic events. Accumulating evidence suggests a link between cancer and arterial thrombosis events. The pathophysiology of arterial thrombosis in cancer is complex and multifactorial. The risk of arterial thrombosis in cancer patients relies on individual risk factors, on cancer-related hypercoagulability, on anticancer drugs and radiotherapy often via a common underlying mechanism of endothelial dysfunction. This review describes the mechanisms involved in the development of arterial thrombotic events and their clinical manifestations. Furthermore, it provides an overview on therapeutic agents associated with arterial thrombosis.Improvements in anti-cancer global strategy resulted into a better outcome of a large percentage of cancer patients many of which experience definitive cure or long-term survival. As a consequence, toxicities claim attention and physicians should also focus on the long-term management of druginduced side effects mainly related to the cardiovascular system. Cancer is a risk factor for both venous (VTEs) and arterial thrombotic (ATEs) events. The risk of VTEs in cancer patients is clearly defined with a roughly 7-fold increase compared to the general population (1).Arterial thrombotic events are increasingly reported in cancer patients both during active treatment and follow-up with various clinical manifestations. The appearance of ATEs is associated with a worse prognosis and a 3-fold increase in overall mortality risk and a probability of recurrent thromboembolism of 37% at six months (2, 3). According to National Cancer Institute's Common Toxicity Criteria, arterial thromboembolism adverse events in cancer patients are related to myocardial ischemia or infarction, cerebral infarction, cerebrovascular accident, cerebral ischemia, ischemic stroke, and peripheral or visceral arterial thrombotic events so highlighting the wide spectrum of possible clinical presentations (4).Tumor cells directly and indirectly induce a state of hypercoagulability through distinct molecular pathways. Platelet activation, increased synthesis of procoagulant factors and reduction of fibrinolytic activity are all triggers for ATEs. Moreover, local and systemic inflammatory stimuli can turn the endothelium into a pro-thrombotic surface. All these mechanisms could be amplified by anticancer drugs and radiotherapy.

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The Impact of Pazopanib on the Cardiovascular System

Cited by 25 publications

References 121 publications

Pazopanib-induced fatal heart failure in a patient with unresectable soft tissue sarcoma and review of literature

Pazopanib-induced fatal heart failure in a patient with unresectable soft tissue sarcoma and review of literature

Molecules and Mechanisms to Overcome Oxidative Stress Inducing Cardiovascular Disease in Cancer Patients

Arterial Thrombosis in Cancer: Spotlight on the Neglected Vessels

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