Mechanism of impaired glucose metabolism during nilotinib therapy in patients with chronic myelogenous leukemia

Ráčil, Zdeněk; Rázga, Filip; Drápalová, J.; Burešová, Lucie; Žáčková, Daniela; Palacková, Martina; Semerád, Lukáš; Malásková, Ludmila; Haluzı́k, Martin; Mayer, Jiřı́

doi:10.3324/haematol.2013.086355

Cited by 66 publications

(62 citation statements)

References 16 publications

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“…47 In addition, nilotinib exerts metabolic effects, including an increase in cholesterol and fasting glucose levels (supplemental Table 3). 17,29,43,67,68 Some patients even develop overt diabetes mellitus. 29,67 All these drug effects are considered to act together to trigger atherosclerosis and VAE development.…”

Section: Potential Mechanisms Underlying Vaes In Tki-treated Patientsmentioning

confidence: 99%

Vascular safety issues in CML patients treated with BCR/ABL1 kinase inhibitors

Valent

Hadzijusufovic

Schernthaner

et al. 2015

Blood

248

219

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Vascular safety is an emerging issue in patients with chronic myeloid leukemia (CML) treated with tyrosine kinase inhibitors (TKIs). Whereas imatinib exhibits a well-documented and favorable long-term safety profile without obvious accumulation of vascular events, several types of vascular adverse events (VAEs) have been described in patients receiving second- or third-generation BCR/ABL1 TKIs. Such VAEs include pulmonary hypertension in patients treated with dasatinib, peripheral arterial occlusive disease and other arterial disorders in patients receiving nilotinib, and venous and arterial vascular occlusive events during ponatinib. Although each TKI interacts with a unique profile of molecular targets and has been associated with a unique pattern of adverse events, the mechanisms of drug-induced vasculopathy are not well understood. Here, recent data and concepts around VAEs in TKI-treated patients with CML are discussed, with special reference to potential mechanisms, event management, and strategies aimed at avoiding occurrence of such events in long-term treated patients.

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Section: Potential Mechanisms Underlying Vaes In Tki-treated Patientsmentioning

confidence: 99%

Vascular safety issues in CML patients treated with BCR/ABL1 kinase inhibitors

Valent

Hadzijusufovic

Schernthaner

et al. 2015

Blood

248

219

View full text Add to dashboard Cite

show abstract

“…The clinical and in vitro studies indicate that perhaps a form of accelerated atherosclerosis could explain at least some of the vascular events seen in patients treated with TKIs. Nilotinib is associated with several metabolic disturbances, including hyperglycemia, perhaps via insulin resistance [50], and dyslipidemia which may develop within as little as three months of treatment [51]. However, these metabolic disturbances certainly do not explain all cases of VAE [52], and probably represent one of the multiple contributory mechanisms.…”

Section: Pathogenesis Of Vaementioning

confidence: 99%

Tyrosine kinase inhibitor associated vascular toxicity in chronic myeloid leukemia

et al. 2015

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Tyrosine kinase inhibitors (TKIs) have revolutionized the management and outcomes of chronic myeloid leukemia (CML) patients. Improved disease control and prolonged life expectancy now mandate focus on improving TKIs' safety profile. Recently, vascular adverse events (VAEs) have emerged as a serious consequence of some of the newer TKIs. In this review, we describe the clinical spectrum of TKI-associated VAE, and examine the unique vascular safety profile of the main TKIs currently used in the treatment of CML: imatinib, nilotinib, dasatinib, bosutinib and ponatinib. The issue of TKI-related platelet dysfunction is discussed as well. We describe the contemporary research findings regarding the possible pathogenesis of the VAE. Finally, the different aspects of TKI-associated VAE management are addressed, including prevention methods, monitoring strategies and treatment options.

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“…Nilotinib has been demonstrated to induce metabolic disturbances, such as hyperglycemia in a substantial proportion of patients, via a mechanism that may involve insulin resistance. 6,17 As high blood cholesterol is a major risk factor for atherosclerotic CVD, 18,19 a clear impact of nilotinib toward lipids has not been published, although dyslipidemia is mentioned as an uncommon side effect by the manufacturer and product instructions advise assessing lipid profile prior to initiating nilotinib therapy and as clinically indicated during treatment. 20 This gap in our knowledge urged us to search for modifications in the plasma lipid profile upon treatment with nilotinib in CML patients without base-line co-medication with lipid-lowering agents.…”

Section: Introductionmentioning

confidence: 99%