Cardiotoxicity of the Anticancer Therapeutic Agent Bortezomib

Abstract

Recent case reports provided alarming signals that treatment with bortezomib might be associated with cardiac events. In all reported cases, patients experiencing cardiac problems were previously or concomitantly treated with other chemotherapeutics including cardiotoxic anthracyclines. Therefore, it is difficult to distinguish which components of the therapeutic regimens contribute to cardiotoxicity. Here, we addressed the influence of bortezomib on cardiac function in rats that were not treated with other drugs. Rats were treated with bortezomib at a dose of 0.2 mg/kg thrice weekly. Echocardiography, histopathology, and electron microscopy were used to evaluate cardiac function and structural changes. Respiration of the rat heart mitochondria was measured polarographically. Cell culture experiments were used to determine the influence of bortezomib on cardiomyocyte survival, contractility,

Bortezomib Induced Congestive Cardiac Failure in a Patient with Multiple Myeloma

“…Bortezomib, by inhibiting ubiquitin-proteasome pathway, would lead to accumulation of ubiquitinated proteins in cardiac myocytes 5 . None of necrotic or apoptotic cells are found in histopathological heart examination and no rise in troponin I levels 6 .…”

I Diretriz Brasileira de Cardio-Oncologia da Sociedade Brasileira de Cardiologia

“…Recomenda-se manter o paciente em normovolemia e utilizar com cautela anti-hipertensivos durante o tratamento com o bortezomibe. Estudo experimental recente demonstra que o bortezomibe pode resultar em disfunção ventricular esquerda, por reduzir a síntese do ATP e reduzir a contratilidade dos cardiomiócitos 236 . Esses dados apontam para a necessidade de monitorização adequada dos pacientes em uso de bortezomibe para a detecção de possível cardiotoxicidade 236 .…”

Cardiac Complications of Cancer Treatment

“…Nowis et al [74] reported that bortezomib treatment leads to left ventricular contractile dysfunction in rats manifested by a significant drop in left ventricle ejection fraction. It is important that in this study rats were not treated with other drugs.…”

“…Dramatic ultrastructular abnormalities of cardiomyocytes, especially within mitochondria, were accompanied by decreased ATP synthesis and decreased cardiomyocyte contractility. [74] Bortezomib induced cardiac effects seem to be reversible. The risk of cardiotoxicity after bortezomib is higher in patients which have previously cardiac problems or being concomitantly treated with other chemotherapeutics including cardiotoxic anthracyclines.…”