Cardiotoxicity induced by tyrosine kinase inhibitors

Orphanos, George; Ioannidis, George N; Ardavanis, Alexandros G

doi:10.1080/02841860903229124

Cited by 246 publications

(196 citation statements)

References 39 publications

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“…16 TKI, although originally considered to be less toxic and better tolerated than other drugs, may also induce cardiac side effects. [19][20][21] Toxicity may result from inhibition of the intended target that is expressed in the heart and the vasculature, e.g. on-target toxicity, or inhibition of alternative targets through limited selectivity, e.g.…”

Section: Discussionmentioning

confidence: 99%

Clinical cardiac safety profile of nilotinib

Kim¹,

Coutre²,

Schwarz³

et al. 2012

Haematologica

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BackgroundNilotinib is a second-generation tyrosine kinase inhibitor with significant efficacy as first-or second-line treatment in patients with chronic myeloid leukemia. Despite preclinical evidence indicating a risk of prolongation of the QT interval, which was confirmed in clinical trials, detailed information on nilotinib's cardiac safety profile is lacking. Design and MethodsHere, we retrospectively assessed cardiovascular risk factors in 81 patients who were being or had previously been treated with nilotinib therapy and evaluated cardiovascular parameters by longitudinal monitoring of the QT interval and left ventricular ejection fraction. Detailed information on the occurrence and management of defined cardiac adverse events was extracted. ResultsThe median duration of nilotinib therapy was 26 months (range, 1-72). The median QT interval at baseline was 413 msec (range, 368-499 msec). During follow-up, the median QT was not significantly different from the baseline value at any time-point. Sixteen of 81 patients (20%) had new electrocardiographic changes. Cardiac function, as assessed by measurement of left ventricular ejection fraction, did not change significantly from baseline at any time-point. During a median follow-up of 44 months (range, 2-73), seven patients (9%), all of whom had received prior imatinib therapy, developed 11 clinical cardiac adverse events requiring treatment. The median time from the start of nilotinib therapy to an event was 14.5 months (range, 2-68). Five of seven patients were able to continue nilotinib therapy with only one brief interruption. ConclusionsWhereas new electrocardiographic abnormalities were recorded in 20% of all patients and some of them developed severe or even life-threatening coronary artery disease, QT prolongation, changes in left ventricular ejection fraction, and clinical cardiac adverse events were uncommon in patients treated with nilotinib.

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Section: Discussionmentioning

confidence: 99%

Clinical cardiac safety profile of nilotinib

Kim¹,

Coutre²,

Schwarz³

et al. 2012

Haematologica

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“…Atualmente é indicado para o tratamento da leucemia mieloide crônica e do linfoma linfoblástico agudo após falência do imatinibe. Os estudos clínicos relatam altas taxas de edema periférico, mas apenas 2% de ocorrência de insuficiência cardíaca e de arritmias 172 .São relatados casos isolados de prolongamento do QT e de derrame pericárdico.…”

Section: -Agentes Biológicosunclassified

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

Filho¹,

Hajjar²,

Bacal³

et al. 2011

Arq. Bras. Cardiol.

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“…It appears that lapatinib therapy is associated with a low prevalence of HF or other adverse CV effects. 31 In clinical studies, LVEF reduced by at least 20% was recorded in only 1.6% and symptomatic HF in 0.2% of patients. The prevalence of cardiotoxic complications was increased in patients having previously received anthracyclines or trastuzumab 32 .…”

Section: Tyrosine Kinase Inhibitorsmentioning

confidence: 99%

Cardiotoxicity due to biological cancer therapy

Gabrić

2017

Cardiologia Croatica

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SAŽETAK: Kardiotoksičnost je sve češća nuspojava onkološkog liječenja pa tako i novijih, bioloških ciljanih lijekova. Posebno razvijena monoklonska protutijela ili inhibitori tirozin-kinaze blokiraju bilo receptore HER-2 bilo VEGF bilo pak aktivnost Abl-kinaze. Međutim, time se ometaju i molekularni mehanzimi ključni za kardiovaskularno zdravlje. Anti-HER2 terapija najčešće uzrokuju reverzibilnu sistoličku disfunkciju lijevog ventrikula, a blokadom VEGF receptora razvija se arterijska hipertenzija i povećava sklonost tromboembolijskim incidentima. Ranim prepoznavanjem i liječenjem bolesnika u kojih se razvila kardiotoksičnost postiže se poboljšanje kliničkih ishoda i kvalitete života, a time je često moguće nastaviti specifično liječenja raka. Pri tome su ključni multidisciplinarni pristup kardiologa i onkologa te redovito kardiološko praćenje.SUMMARY: Cardiotoxicity has been increasingly reported as a side effect of oncologic treatment, including novel targeted biological therapy. Specific monoclonal antibodies or tyrosine kinase inhibitors have been developed for blockade of HER2 receptors, VEGF receptors, or Abl kinase activity. However, these actions also interfere with molecular mechanisms that are crucial for cardiovascular health. Anti HER2 therapy generally induces reversible systolic left ventricular dysfunction, whereas VEGF receptor blockade leads to development of arterial hypertension and increased susceptibility to thromboembolic events. In patients developing cardiotoxicity, better clinical outcome and quality of life can be achieved by early recognition and treatment, thus also enabling continuation of anti-cancer therapy in many cases. A multidisciplinary approach including cardiologists and oncologists, along with regular cardiologic follow up, is crucial for successful patient management.KLJUČNE RIJEČI: kardiotoksičnost, kardioonkologija, biološka terapija tumora, inhibitori tirozin-kinaze.

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Cardiotoxicity induced by tyrosine kinase inhibitors

Cited by 246 publications

References 39 publications

Clinical cardiac safety profile of nilotinib

Clinical cardiac safety profile of nilotinib

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

Cardiotoxicity due to biological cancer therapy

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