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      Monitoring for Chemotherapy-Related Cardiotoxicity in the Form of Left Ventricular Systolic Dysfunction: A Review of Current Recommendations

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          Abstract

          Cardiotoxicity is a well-established complication of multiple cancer therapeutics, and the one of the most prominent effects that limits the use of these agents is in the form of left ventricular dysfunction, otherwise known as chemotherapy-induced cardiomyopathy (CIMP). Because CIMP can worsen patient outcomes and interfere with a patient's life-saving cancer treatments, it is important to implement a monitoring strategy for patients undergoing potentially cardiotoxic treatments. Efforts have been made by multiple societies to provide recommendations for screening and monitoring for CIMP in at-risk patients, with slight variations between guideline documents and expert consensuses. Most of the recommendations for monitoring for CIMP are specific to anthracyclines and the human epidermal growth factor receptor 2-antagonist trastuzumab, with very limited guidance for other cardiotoxic agents such as Tyr kinase inhibitors and proteasome inhibitors, which we cover in this article. Echocardiography remains the mainstay for imaging surveillance because of its safety profile and widespread availability, but the accuracy of cardiac magnetic resonance imaging (CMR) makes it an important modality when there are discrepancies in left ventricular ejection fraction assessment. Subclinical cardiotoxicity may be detected using laboratory biomarkers such as cardiac troponin and brain natriuretic peptide as well as myocardial deformation (strain) imaging by echocardiography or CMR. Specific recommendations for timing and frequency of laboratory biomarker assessment remain up for debate, but myocardial deformation imaging should be performed with every echocardiogram or CMR assessment. Future studies are needed to evaluate the efficacy of established surveillance recommendations and to develop specific recommendations for novel cancer therapeutics.

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          Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging.

          The rapid technological developments of the past decade and the changes in echocardiographic practice brought about by these developments have resulted in the need for updated recommendations to the previously published guidelines for cardiac chamber quantification, which was the goal of the joint writing group assembled by the American Society of Echocardiography and the European Association of Cardiovascular Imaging. This document provides updated normal values for all four cardiac chambers, including three-dimensional echocardiography and myocardial deformation, when possible, on the basis of considerably larger numbers of normal subjects, compiled from multiple databases. In addition, this document attempts to eliminate several minor discrepancies that existed between previously published guidelines. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.
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            2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). Developed with the special contribution of the Heart Failure Association (HFA) of the ESC.

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              Osimertinib or Platinum–Pemetrexed in EGFR T790M–Positive Lung Cancer

              Background Osimertinib is an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) that is selective for both EGFR-TKI sensitizing and T790M resistance mutations in patients with non-small-cell lung cancer. The efficacy of osimertinib as compared with platinum-based therapy plus pemetrexed in such patients is unknown. Methods In this randomized, international, open-label, phase 3 trial, we assigned 419 patients with T790M-positive advanced non-small-cell lung cancer, who had disease progression after first-line EGFR-TKI therapy, in a 2:1 ratio to receive either oral osimertinib (at a dose of 80 mg once daily) or intravenous pemetrexed (500 mg per square meter of body-surface area) plus either carboplatin (target area under the curve, 5 [AUC5]) or cisplatin (75 mg per square meter) every 3 weeks for up to six cycles; maintenance pemetrexed was allowed. In all the patients, disease had progressed during receipt of first-line EGFR-TKI therapy. The primary end point was investigator-assessed progression-free survival. Results The median duration of progression-free survival was significantly longer with osimertinib than with platinum therapy plus pemetrexed (10.1 months vs. 4.4 months; hazard ratio; 0.30; 95% confidence interval [CI], 0.23 to 0.41; P<0.001). The objective response rate was significantly better with osimertinib (71%; 95% CI, 65 to 76) than with platinum therapy plus pemetrexed (31%; 95% CI, 24 to 40) (odds ratio for objective response, 5.39; 95% CI, 3.47 to 8.48; P<0.001). Among 144 patients with metastases to the central nervous system (CNS), the median duration of progression-free survival was longer among patients receiving osimertinib than among those receiving platinum therapy plus pemetrexed (8.5 months vs. 4.2 months; hazard ratio, 0.32; 95% CI, 0.21 to 0.49). The proportion of patients with adverse events of grade 3 or higher was lower with osimertinib (23%) than with platinum therapy plus pemetrexed (47%). Conclusions Osimertinib had significantly greater efficacy than platinum therapy plus pemetrexed in patients with T790M-positive advanced non-small-cell lung cancer (including those with CNS metastases) in whom disease had progressed during first-line EGFR-TKI therapy. (Funded by AstraZeneca; AURA3 ClinicalTrials.gov number, NCT02151981 .).
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                Author and article information

                Contributors
                (View ORCID Profile)
                Journal
                JCO Oncology Practice
                JCO Oncology Practice
                American Society of Clinical Oncology (ASCO)
                2688-1527
                2688-1535
                May 2021
                May 2021
                : 17
                : 5
                : 228-236
                Affiliations
                [1 ]Department of Internal Medicine, Section of Cardiology, University of Nebraska Medical Center, Omaha, NE
                [2 ]Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE
                [3 ]Loma Linda University Cancer Center, Loma Linda, CA
                Article
                10.1200/OP.20.00924
                33689453
                33a518e7-9a20-4c8d-9eca-1df18b04f05f
                © 2021
                History

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