Cardiac dysfunction induced by novel targeted anticancer therapy: An emerging issue

Abstract

Increasing use of targeted anticancer agents that inhibit tyrosine kinase signaling (monoclonal antibodies or tyrosine kinase inhibitors) has dramatically improved the survival of patients with malignancies. However, cardiotoxicity, including heart failure, left ventricular dysfunction, hypertension, myocardial infarction, and thromboembolism, has occurred. Importantly, these cardiotoxicities are at least partially reversible and responsive to medical management. Early recognition of cardiovascular side effects is vital to allow long-term, continuous therapy with these life-prolonging agents. This article reviews potential cardiovascular side effects of frequently used inhibitors of tyrosine kinase activity (eg, trastuzumab, sunitinib) and discusses the diagnosis and management of cardiotoxicity associated with targeted therapy.

Noncardiac Vascular Toxicities of Vascular Endothelial Growth Factor Inhibitors in Advanced Cancer: A Review

“…Angiotensin II inhibitors, diuretics, hydropyridine calcium channel blockers (CCBs), and ␤-blockers are also possible antihypertensive agents. The nondihydropyridine CCBs (verapamil and diltizamen) are cytochrome P450 (CYP)3A4 inhibitors so are used cautiously in conjunction with VEGFIs metabolized by the CYP3A4 pathway [44,45].…”

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

“…Ela inibe duas quinases pró-apoptóticas, ASK1 e MST2 que são importantes na injúria por estresse oxidativo, gerando apoptose do miócito. A ocorrência de hipertensão pode ser atribuída à inibição dos receptores de VEGF 179 . Apesar de não ser tão comum, a cardiotoxicidade do sorafenibe pode ser grave e levar à morte.…”

Regarding: ‘Costs of managing adverse events in the treatment of first-line metastatic renal cell carcinoma: bevacizumab in combination with interferon-α2a compared with sunitinib’

“…Moreover, toxicities such as hypothyroidism and cardiotoxicity may have been grossly underestimated in the sunitinib registrative trial (Motzer et al, 2007) compared with the levels indicated from other recent studies of sunitinib (Rini et al, 2007;Chen, 2009;Torino et al, 2009;Di Lorenzo et al, 2009), whereas the safety profile of bevacizumab plus interferon does not seem to have changed so much over time. When considering these additional facts, the indirect economic advantage of bevacizumab plus interferon seems to be even more evident and convincing.…”