Rapid and life-threatening heart failure induced by pazopanib

Abstract

A 70-year-old man with history of stage IV renal cell carcinoma, chronic atrial fibrillation on warfarin, coronary artery disease status post-percutaneous coronary intervention resulting in an ischaemic cardiomyopathy with left ventricular ejection fraction of 40%–45%, presented with shortness of breath 10 days after starting pazopanib. Within the first week of starting pazopanib, the patient developed fatigue and progressive dyspnoea on exertion. His symptoms quickly worsened and he had compromised mental status. He was transferred to the intensive care unit (ICU) and intubated due to continued respiratory distress. He was found to be in cardiogenic shock and was started on inotropic support with dobutamine and norepinephrine. With maximum support, the patient was slowly weaned off vasopressors and was successfully extubated on ICU day 9. His hospital stay lasted 29 days with management of multiple medical complications, and he was eventually discharged to a rehabilitation facility.

The real-life outcome of pazopanib in patients with advanced soft tissue sarcoma: A retrospective cross-sectional study of a Turkish cohort

“…However, fatal heart failure that occurred in one of our patients is rare in the literature and should be kept in mind in the follow-up of patients. 9,19,20 Besides, we would like to emphasize that our patients who could not continue treatment due to severe toxicity had shorter PFS. Nevertheless, the results of our study about adverse effects are not sufficient because the adverse effects listed in our patients' files were mostly based on laboratory parameters.…”

Incidence of heart failure following exposure to a protein kinase inhibitor, a French population‐based study

“…Other studies have shown an increased risk of HF in patients exposed to sunitinib and sorafenib, while some case reports describe the impact of pazopanib on HF occurrence among sarcoma patients. [11][12][13][14][15][16] In a scientific statement, the American Heart Association classified lapatinib, imatinib, sunitinib and sorafenib as carrying moderate to minor risks of HF. 17 The primary objective of the current study was to identify the PKIs most frequently associated with an HF outcome.…”

“…However, this study suffers from typical limitations of pharmacovigilance studies such as under‐ and selective reporting. Other studies have shown an increased risk of HF in patients exposed to sunitinib and sorafenib, while some case reports describe the impact of pazopanib on HF occurrence among sarcoma patients 11–16 . In a scientific statement, the American Heart Association classified lapatinib, imatinib, sunitinib and sorafenib as carrying moderate to minor risks of HF 17 …”

Fatal Heart Failure Induced By Pazopanib In A Sarcoma Patient Previously Treated With Gemcitabine

“…Although rare, gemcitabine therapy can cause cardiotoxicity in the form of acute congestive heart failure [ 4 ]. On the other hand pazopanib is a an oral multi-targeted tyrosine kinase inhibitor (TKI), targeting vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF) and stem cell factor (c-KIT) receptors [ 5 , 6 ]. It is approved for the treatment of metastatic renal cell carcinoma (RCC) and soft tissue sarcoma [ 5 , 6 ].…”

“…The main side effects are fatigue, nausea, diarrhoea and arterial hypertension. The increased use of TKI agents has been associated with recognition of a potentially fatal spectrum of toxicities, including cardiotoxicity, sometimes even fatal [ 6 , 7 ].…”