Symptomatic Sinus Bradycardia in a Patient with Solitary Fibrous Tumor/Hemangiopericytoma Treated with Pazopanib

Abstract

Pazopanib, a multi-targeted tyrosine kinase inhibitor, is associated with cardiovascular adverse events, such as hypertension, cardiac dysfunction, and thromboembolism. However, symptomatic pazopanib-related bradycardia is uncommon. We herein report a case of symptomatic bradycardia of 35 beats per minute in a patient with solitary fibrous tumor/hemangiopericytoma (SFT/HPC) treated with pazopanib for 1 month. His heart rate recovered to a normal range soon after pazopanib cessation. He restarted pazopanib at a reduced dose, which was continued without SFT/HPC progression or bradycardia recurrence. This case highlights the possibility of bradycardia induced by pazopanib and the importance of monitoring the patient's heart rate.

Oral Oncolytics and Cardiovascular Risk Management and Monitoring

“…The proposed pharmacologic mechanism and associated oral cancer therapies are reviewed below and further outlined in Table 1. [14][15][16][17][18][19][20][21][22][23][24][25]…”

“…29,30 However, bradycardia is believed to be a result of multiple physiologic alterations from targeted therapies and therefore can be seen with other targeted oncolytics such as the VEGF receptor inhibitor pazopanib, the immunomodulator thalidomide, the mitogen-activated protein kinase (MEK) inhibitor trametinib, and the oral Breakpoint Cluster Region -Abelson murine Leukemia (BCR-ABL) inhibitor ponatinib. 2,15,16,31 Risk factors for bradycardia with oral oncolytic therapy include advanced age, coronary artery disease, decreased systolic function, and a baseline heart rate less than 70 BPM. 14,31 Mechanisms contributing to bradycardia vary based on the oral oncolytic and are described in Table 1.…”

“…14,31 Mechanisms contributing to bradycardia vary based on the oral oncolytic and are described in Table 1. [14][15][16][17][18][19][20][21][22][23][24][25] The primary mechanism for bradycardia with oral oncolytics is the inhibition of hyperpolarization-activated cyclic nucleotide-gated channel 4 activity. Hyperpolarizationactivated cyclic nucleotide-gated channel 4 activity plays a significant role in the sinoatrial node to set and regulate the intrinsic heart rate, specifically the lower limit of the heart rate range, and protects the stability of the sinoatrial node during autonomic nervous system activity.…”

“…32 Additional mechanisms of bradycardia from oral oncolytic therapy include decreased testosterone from hypogonadism, dysfunction of the autonomic nervous system by pazopanib, and alteration in the dorsal motor neuron of the vagus nerve through tumor necrosis factor alpha inhibition by thalidomide. [14][15][16]…”

“…[34][35][36][37][38][39][40][41][42][43][44][45][46] There are multiple proposed mechanisms for altered cholesterol levels with targeted cancer treatment, with the most known and prevalent described here and further outlined in Table 1. [14][15][16][17][18][19][20][21][22][23][24][25] The inhibition of mTOR, a serine-threonine protein kinase that mediates cellular growth, proliferation, differentiation, and angiogenesis, results in reduced lipase activity. This reduced lipase activity further results in dyslipidemia through reduced catabolism of lipoproteins in plasma.…”