The use of imatinib mesylate has no adverse effects on the heart function. Results of a pilot study in patients with chronic myeloid leukemia

Marcolino, Milena Soriano; Ribeiro, Antônio Luiz Pinho; Clementino, Nelma Cristina D.; Nunes, Maria do Carmo Pereira; Barbosa, Márcia M.; Silva, Maria Helena C.R.; Bittencourt, Henrique; Geleijnse, Marcel L.; Boersma, Eric

doi:10.1016/j.leukres.2010.07.011

Cited by 11 publications

(10 citation statements)

References 34 publications

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“…22 Previous reports described cardiotoxicity resulting from therapy with sunitinib, 23,24 sorafinib, 24 and imatinib mesylate. 25 Although the clinical occurrence and/or significance of the latter are being disputed, [26][27][28][29][30][31][32][33] reengineering efforts have been undertaken to alleviate the problem. 34 More recently, QTc prolongation and myocardial infarction related to dasatinib therapy have been reported.…”

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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“…Though initial reports suggested that inhibition of Abl kinase by imatinib leads to mitochondrial damage and cardiac myocyte cell death in both animal models and humans [78], more recent data suggests that this effect is only seen at very high doses that are not likely to be clinically relevant [79, 80]. In 3 clinical trials, no significant cardiac toxicity was seen with imatinib, even with up to 12 months of therapy and over 3 years of follow up [81-83]. However, the manufacturer reported retrospective data suggesting a rate of 0.2% of cardiotoxicity [84], thus it is still recommended that patients undergo cardiac monitoring (especially of LV function) during and after imatinib therapy [85].…”

Section: Molecular Targets: Classifications Currently Approved Drugsmentioning

confidence: 99%

Cardiotoxicity of Molecularly Targeted Agents

Hedhli¹,

Russell²

2012

CCR

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Cardiac toxicity of molecularly targeted cancer agents is increasingly recognized as a significant side effect of chemotherapy. These new potent therapies may not only affect the survival of cancer cells, but have the potential to adversely impact normal cardiac and vascular function. Unraveling the mechanisms by which these therapies affect the heart and vasculature is crucial for improving drug design and finding alternative therapies to protect patients predisposed to cardiovascular disease. In this review, we summarize the classification and side effects of currently approved molecularly targeted chemotherapeutics.

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“…The 8-year probability of grade 3-4 cardiac, vascular, or congestive heart failure (CHF) AEs with imatinib was 0.5%, 0.3%, or 3.1%, respectively. 10 The relative frequencies of vascular 5,[11][12][13][14][15][16][17][18] and cardiac [19][20][21][22][23][24][25][26] AEs with the different TKIs are difficult to estimate based on the literature because different reports have used different methods for analysis, and what events are included in the general category of "arteriothrombotic events" vary widely, with some reports analyzing a few hundred medical dictionary for regulatory activities (MeDRA) terms while others focus only on specific confirmed diagnosis.…”

Section: Introductionmentioning

confidence: 99%

Analysis of cardiovascular and arteriothrombotic adverse events in chronic-phase CML patients after frontline TKIs

Jain¹,

Kantarjian²,

Boddu³

et al. 2019

Blood Advances

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Cardiovascular or arteriothrombotic adverse events (CV- or AT-AEs) are reported in chronic myeloid leukemia (CML) patients treated with tyrosine kinase inhibitors (TKIs). The incidence and characteristics across different TKI have not been systematically analyzed. We analyzed 531 patients treated with frontline TKIs in different prospective trials: imatinib 400 mg (n = 71) and 800 mg (n = 203), nilotinib (n = 108), dasatinib (n = 106), and ponatinib (n = 43). Characteristics and incidence of new-onset CV-AEs and AT-AEs were analyzed. Poisson regression models assessed factors associated with AE incidence. Median follow-up was 94 months (range, 2-195). Overall, 237 patients (45%) developed CV-AEs and 46 (9%) developed AT-AEs. Hypertension was the most common AE seen in 175 patients (33%; grade 3/4 in 17%). CV-AE and AT-AE incidence ratios (IRs) with 95% confidence intervals (CIs) were 8.6 (7.6-9.8) and 1.7 (1.2-2.2) per 100 person-years. Among the TKIs, ponatinib showed the highest IR (95% CI) for CV-AEs and AT-AEs at 40.7 (27.9-59.4) and 9.0 (4.1-20.1). In multivariate analysis, ponatinib therapy was associated with increased incidence rate ratio (IRR) for CV-AEs (4.62; 95% CI, 2.7-7.7; P < .0001) and AT-AEs (6.38; 95% CI, 1.8-21.8; P < .0001) compared with imatinib 400. In summary, there is an increased risk of CV-AEs (except hypertension) and AT-AEs in CML patients treated with newer TKIs, particularly with ponatinib. Patients on TKIs must be informed and closely monitored for vascular AEs. These studies were registered at www.clinicaltrials.gov as #NCT00048672, #NCT00038649, #NCT00050531, #NCT00254423, #NCT00129740, and #NCT01570868.

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The use of imatinib mesylate has no adverse effects on the heart function. Results of a pilot study in patients with chronic myeloid leukemia

Cited by 11 publications

References 34 publications

Clinical cardiac safety profile of nilotinib

Clinical cardiac safety profile of nilotinib

Cardiotoxicity of Molecularly Targeted Agents

Analysis of cardiovascular and arteriothrombotic adverse events in chronic-phase CML patients after frontline TKIs

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