Anticancer therapy-induced vascular toxicity: VEGF inhibition and beyond

Lisi, Daniela Di; Madonna, Rosalinda; Zito, Concetta; Bronte, Enrico; Badalamenti, Giuseppe; Parrella, Paolo; Monte, Ines; Tocchetti, Carlo G.; Russo, Antonio; Novo, Giuseppina

doi:10.1016/j.ijcard.2016.11.174

Cited by 67 publications

(36 citation statements)

References 98 publications

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“…For some drugs, such as anthracyclines, 5‐fluorouracil and capecitabine, the HER2 targeting antibody trastuzumab, and VEGF‐directed tyrosine kinase inhibitors, the potential of cardiac damage is particularly high . These drugs can cause (or aggravate) left ventricular systolic or diastolic dysfunction and may precipitate myocardial ischaemia and arrhythmias by a variety of mechanisms ( Table ) . Hence, their use in patients with pre‐existing HF must be extremely cautious, justified by the benefit to cancer outcomes and the absence of alternative oncological treatments, and with appropriate informed consent and close surveillance with clinical assessment, cardiac imaging and biomarkers.…”

Section: Challenges In Cancer Therapy For Patients With Pre‐existing mentioning

confidence: 99%

Cancer diagnosis in patients with heart failure: epidemiology, clinical implications and gaps in knowledge

Ameri

Canepa

Anker

et al. 2018

European J of Heart Fail

145

130

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Cancer and heart failure (HF) are common medical conditions with a steadily rising prevalence in industrialized countries, particularly in the elderly, and they both potentially carry a poor prognosis. A new diagnosis of malignancy in subjects with pre-existing HF is not infrequent, and challenges HF specialists as well as oncologists with complex questions relating to both HF and cancer management. An increased incidence of cancer in patients with established HF has also been suggested. This review paper summarizes the epidemiology and the prognostic implications of cancer occurrence in HF, the impact of pre-existing HF on cancer treatment decisions and the impact of cancer on HF therapeutic options, while providing some practical suggestions regarding patient care and highlighting gaps in knowledge.

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Section: Challenges In Cancer Therapy For Patients With Pre‐existing mentioning

confidence: 99%

Cancer diagnosis in patients with heart failure: epidemiology, clinical implications and gaps in knowledge

Ameri

Canepa

Anker

et al. 2018

European J of Heart Fail

145

130

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“…In fact, several studies have revealed that anthra-DOI: 10.1159/000505486 cyclines or other anticancer drugs have cardiotoxic effects [1]. Target therapy can also cause cardiotoxicity, but it is not clear how big this problem is [2]. Tyrosine kinase inhibitors (TKIs) are selective, and for this reason they should be less cardiotoxic than other drugs.…”

Section: Introductionmentioning

confidence: 99%

Cardiovascular Toxicity in Cancer Patients Treated with Tyrosine Kinase Inhibitors: A Real-World Single-Center Experience

et al. 2020

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Background: Target therapy can cause various cardiovascular complications. The aim of this study was to evaluate the burden of cardiovascular complications related to treatment with anti-BCR-ABL tyrosine kinase inhibitors (TKIs) and to determine if there are differences between the latest-and firstgeneration TKIs. Methods: A retrospective observational study was carried out on 55 patients (39 men, 16 women; mean age ± SD: 58 ± 11 years) treated with TKIs targeting Bcr-Abl for a median period of 3.5 years. Patients were divided in two groups according to the type of treatment. Group A included patients treated with latest-generation TKI (nilotinib, dasatinib, and ponatinib), while group B included patients treated with first-generation TKI (imatinib). Cardiological evaluation included electrocardiogram, echocardiogram with global longitudinal strain of left ventricle (GLS), and carotid ultrasound scan with arterial stiffness measurement (pulse wave velocity, PWV). Adverse cardiovascular events were recorded in both groups. Results: Statistical analysis showed that cardiovascular adverse events (myocardial ischemia, peripheral artery disease, deep vein thrombosis, and pleural effusion) were significantly more frequent in group A than group B (p value = 0.044). Moreover, there was a significant reduction in GLS and PWV in group A when compared to group B (respectively, p = 0.03 and p = 0.004). Conclusions:Our study confirms that imatinib is a relatively safe drug, while it reveals that the latest-generation TKIs may cause a burden of cardiovascular complications. GLS and PWV allow detection of early signs of cardiac and vascular toxicity in oncohematologic patients treated with TKI, and their use is advisable.

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“…Anthracycline chemotherapy induces oxidative stress that is toxic to the vascular endothelium [37,38]. Endothelial injury reduces the ability of the vessels to vasodilate and greatly increases susceptibility to accelerated atherosclerosis; hence, FMD is a strong predictor of cardiovascular events [24,25].…”

Section: Discussionmentioning

confidence: 99%

Early markers of cardiovascular injury in childhood leukaemia survivors treated with anthracycline chemotherapy

et al. 2019

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Background: Cardiovascular disease (CVD) is the leading non-malignant cause of death in childhood cancer survivors. Heightened risk of CVD is often attributable to treatment with anthracycline chemotherapy. Anthracyclinemediated cardiac injury may lie latent for years following cessation of treatment and is therefore often not detected until disease is advanced and aggressive therapy is required. Symptomatic CVD may be preceded by subclinical cardiac and vascular dysfunction. This study aimed to determine whether such dysfunction could be detected in healthy, anthracycline-treated survivors of childhood leukaemia. Methods: Cardiac magnetic resonance imaging (cMRI) with late gadolinium enhancement and endothelial function were used to characterise pre-clinical stages of CVD. Twenty-two long-term (>5 years survival; age 21 ± 3 years) childhood leukaemia survivors were assessed. All survivors were asymptomatic and had normal resting echocardiography. To exclude potential confounding effects of radiotherapy, no survivors had received this treatment. Twenty-two similarly aged (25 ± 3 years) gender-matched controls were recruited for comparison. Results: Left ventricular ejection fraction was lower in the survivors (55.0 ± 4.6%) compared to the controls (59.4 ± 6.2%; p = 0.010). Further, five survivors (23%) had clinically reduced (<50%) left ventricular ejection fraction. Normalised left ventricular end systolic volume was augmented in survivors (40.0 ± 9.1 mL·m 2 vs. 34.5 ± 7.5 mL·m 2 ; p = 0.038). Cardiac MRI did not show any late gadolinium enhancement. High resolution, ultrasound-derived flow mediated dilation was impaired in survivors (6.7 ± 2.1% vs. 8.60 ± 1.91%, p = 0.005). Conclusions: We detected subclinical changes in cardiovascular structure and function indicative of early disease in anthracycline-treated childhood leukaemia survivors with normal echocardiography. Early detection and characterisation of underlying disease allows for timely intervention and improved outcomes in this at-risk population.

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Anticancer therapy-induced vascular toxicity: VEGF inhibition and beyond

Cited by 67 publications

References 98 publications

Cancer diagnosis in patients with heart failure: epidemiology, clinical implications and gaps in knowledge

Cancer diagnosis in patients with heart failure: epidemiology, clinical implications and gaps in knowledge

Cardiovascular Toxicity in Cancer Patients Treated with Tyrosine Kinase Inhibitors: A Real-World Single-Center Experience

Early markers of cardiovascular injury in childhood leukaemia survivors treated with anthracycline chemotherapy

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