Heart failure associated with sunitinib malate

Abstract

BACKGROUND. Sunitinib malate is a novel multitargeted receptor tyrosine kinase inhibitor with established efficacy in the treatment of metastatic renal cell carcinoma and imatinib‐resistant gastrointestinal stromal tumor. This report describes the development of heart failure in cancer patients who received this novel agent. METHODS. A retrospective study was conducted at M. D. Anderson Cancer Center during a 1‐year period on patients who received sunitinib and developed heart failure. RESULTS. During 2006, 6 of 224 (2.7%) patients who received sunitinib developed heart failure (HF) that resulted in substantial morbidity and, in some cases, mortality. Symptomatic heart failure occurred soon after initiation of sunitinib (mean onset 22 days after initiation), was associated with decline in cardiac function and elevations in blood pressure, and was not completely reversible in most patients, even after termination of sunitinib therapy. CONCLUSIONS. These observations suggested that sunitinib‐associated heart failure may represent a potentially serious toxicity and underscore the need for careful monitoring of cardiac function and aggressive control of hypertension in these patients. Studies to elucidate potential mechanisms of heart failure and left ventricular dysfunction resulting from treatment with sunitinib are necessary to develop strategies for prevention and treatment of this complication. Cancer 2008. ©2008 American Cancer Society.

Toxic cardiomyopathy leading to fatal acute cardiac failure related to vandetanib: a case report with histopathological analysis

“…In fact, the heart histological findings are similar to those reported in TKItreated rats, which show myocardial fibrosis and degeneration and suggest chronic aggression toward myocardial tissue (12). Of note, cardiomyocyte hypertrophy was also described in endomyocardial biopsies of two patients with sunitinib-associated CHF while transmission electron microscopy demonstrated aberrantly shaped, swollen mitochondria (11,14).…”

Cardio-Oncology

“…59 Preclinical models of toxicity have demonstrated effects of TKIs on mitochondrial injury and cardiomyocyte apoptosis in both mice and cultured rat cardiomyocytes. 58,60 TKIs inhibit several tyrosine kinases, including adenosine monophosphate-activated protein kinase (AMPK) and platelet-derived growth factor (PDGFR; Figure 2), which may explain the higher rate of clinical cardiac toxicity than more selective VEGF-targeted therapies. Mice lacking PDGF receptor expression respond to pressure overload induced by surgical aortic constriction with accelerated cardiac remodeling and with impaired vascular growth and function.…”

“…Persistent cardiac dysfunction has been noted in some people treated with sunitinib. 60,61 At least one case of fatal cardiac dysfunction has been reported with axitinib, 57,59 a TKI designed against mutant gene BCR-ABL1 (breakpoint cluster regionAbelson 1 gene) that also has inhibitory effects on VEGF and PDGF. Larger meta-analyses have found cardiac dysfunction and HF to be a common problem with TKIs, and more work is needed to help discern appropriate screening and monitoring for cardiotoxicity.…”

Review: Targeted therapy in renal cancer

“…Laboratory abnormalities described for sunitinib treated patients were neutropenia, anemia, and thrombocytopenia. There was a 13% incidence of left ventricular dysfunction in the sunitinib arm compared to 3% with interferon-a [Motzer et al 2007b] and patients treated with sunitinib should be monitoring with echocardiography or nuclear-labeled LVEF assessment at baseline and periodically during treatment [Khakoo et al 2008;Telli et al 2008;Chu et al 2007]. Thyroid function anomalies are also common with sunitinib therapy, with hypothyroidism being relatively common and transient hyperthyroidism reported .…”