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

Abstract

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.

Cardiac Safety of Pegylated Liposomal Doxorubicin After Conventional Doxorubicin Exposure in Patients With Sarcoma and Breast Cancer

“…This patient was able to receive three cycles of PLD prior to the cardiac event. It is uncertain if PLD was the sole contributing factor for this cardiac event, as this patient had a lower baseline LVEF of 50%-55% and was previously on pazopanib, another known agent that may cause cardiotoxicity [ 19 , 20 ]. The most common cardiotoxic agents used in the sarcoma group were pazopanib and ifosfamide.…”

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

“…Current data regarding the risk of HF occurrence following PKI exposure are sparse. Some case reports describe the relevance of pazopanib in the occurrence of HF in patients with sarcoma 11–14 . The American Heart Association classified certain PKIs according to their ability to induce or precipitate HF based on published clinical trials 17 .…”

“…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 …”