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Trastuzumab cardiotoxicity

Martino Deidda, Rosalinda Madonna, Ruggiero Mango, Pasquale Pagliaro, Pier P Bassareo, Lucia Cugusi, Silvio Romano, Maria Penco, Francesco Romeo, Giuseppe Mercuro
Despite advances in supportive and protective therapy for myocardial function, heart failure caused by various clinical conditions, including cardiomyopathy due to antineoplastic therapy, remains a major cause of morbidity and mortality. Because of the limitations associated with current therapies, investigators have been searching for alternative treatments that can effectively repair the damaged heart and permanently restore its function. Damage to the heart can result from both traditional chemotherapeutic agents, such as anthracyclines, and new targeted therapies, such as trastuzumab...
May 2016: Journal of Cardiovascular Medicine
Katarzyna Rygiel
Advances in oncologic therapies have allowed many patients with breast cancer to achieve better outcomes and longer survival. However, this progress has been tempered by cardiotoxicity, associated with anticancer therapies, ranging from subclinical abnormalities to irreversible life-threatening complications, such as congestive heart failure or cardiomyopathy. In particular, exposure to chemotherapy (CHT), including anthracyclines and trastuzumab, can lead to cardiac dysfunction with short- or long-term consequences, among patients with breast cancer...
September 2016: Indian Journal of Pharmacology
Balazs T Nemeth, Zoltan V Varga, Wen Jin Wu, Pal Pacher
Epidermal growth factor receptor-2 (HER-2) is overexpressed in 20% to 25% of human breast cancers, which is associated with aggressive tumor growth and poor prognosis. Trastuzumab (Herceptin®) is a humanized monoclonal antibody directed against HER-2, the first highly selective form of therapy targeting HER-2 overexpressing tumors. Although initial trials indicated high efficacy and a favorable safety profile of the drug, the first large, randomized trial prompted a retrospective analysis of cardiac dysfunction in prior trials utilizing trastuzumab...
October 7, 2016: British Journal of Pharmacology
Hsiao-Hsuan Kuo, Wei-Wu Chen
Human epidermal growth factor receptor (HER2)-positive breast cancer is associated with a more aggressive disease and poor prognosis. The development of trastuzumab, a HER2-targeted agent, has changed the paradigm of HER2-positive breast cancer treatment and improved survival rates dramatically. However, metastatic HER2-positive breast cancer patients eventually develop resistance to this treatment regimen eventually. A new anti-HER2 antibody-drug conjugate, Trastuzumab emtansine (T-DM1), has been shown to improve treatment efficacy...
October 2016: Hu Li za Zhi the Journal of Nursing
S Yuce Sari, G Yazici, M A Sendur, K Altundag, M Gultekin, F Yildiz, G Ozyigit
No abstract text is available yet for this article.
October 1, 2016: International Journal of Radiation Oncology, Biology, Physics
Vineet Goyal, Hilary Bews, David Cheung, Sheena Premecz, Soma Mandal, Bilal Shaikh, Ryan Best, Rahul Bhindi, Rakesh Chaudhary, Amir Ravandi, James Thliveris, Pawan K Singal, Saroj Niraula, Davinder S Jassal
BACKGROUND: In the breast cancer setting, anticancer therapies including doxorubicin (DOX) and trastuzumab (TRZ) are associated with a significantly increased risk of cardiotoxicity. Despite the increasing support for the role of oxidative stress (OS) in its pathophysiology, we still do not have an optimal antioxidant for the prevention of DOX + TRZ-mediated cardiac dysfunction. The objective of this study was to investigate whether the novel antioxidant N-acetylcysteine amide (NACA) can attenuate DOX + TRZ-induced heart failure in a murine model...
June 20, 2016: Canadian Journal of Cardiology
Edith Pituskin, Mark Haykowsky, Margaret McNeely, John Mackey, Neil Chua, Ian Paterson
BACKGROUND: Cancer is the leading cause of premature death in Canada. In the last decade, important gains in cancer survival have been achieved by advances in adjuvant treatment. However, many oncologic treatments also result in cardiovascular "toxicity". Furthermore, cardiac risk factors such as hypertension, dyslipidemia, and diabetes mellitus are known to contribute to the progression of cardiac damage and clinical cardiotoxicity. As such, for many survivors, the risk of death from cardiac disease exceeds that of recurrent cancer...
September 15, 2016: BMC Cancer
A King, J Thambyrajah, E Leng, M J Stewart
Herceptin (Trastuzumab) is a widely used and effective drug for the treatment of Her2+ breast cancer but its cardiotoxic side effects require regular monitoring by echocardiography. A 10% reduction in left ventricular ejection fraction can lead to suspension of treatment and therefore has significant implications for patient prognosis in terms of cardiac and cancer outcomes. Assessment of LV function by conventional 2D biplane method of discs (2DEF) has limitations in accuracy and reproducibility. Global longitudinal strain (GLS) is becoming more widely available and user friendly...
September 2016: Echo Research and Practice
Tarek Magdy, Brian T Burmeister, Paul W Burridge
The cardiotoxicity of certain chemotherapeutic agents is now well-established, and has led to the development the field cardio-oncology, increased cardiac screening of cancer patients, and limitation of patients' maximum cumulative chemotherapeutic dose. The effect of chemotherapeutic regimes on the heart largely involves cardiomyocyte death, leading to cardiomyopathy and heart failure, or the induction of arrhythmias. Of these cardiotoxic drugs, those resulting in clinical cardiotoxicity can range from 8 to 26% for doxorubicin, 7-28% for trastuzumab, or 5-30% for paclitaxel...
September 5, 2016: Pharmacology & Therapeutics
Edward T H Yeh, Hui-Ming Chang
Importance: Oncocardiology is a medical discipline that focuses on the identification, prevention, and treatment of cardiovascular complications related to cancer therapy. This discipline has gained interest from the cardiology community in recent years because of a remarkable increase in the number of cancer survivors and the proliferation of new cancer therapies causing cardiovascular complications, such as hypertension, heart failure, vascular complications, and cardiac arrhythmia...
August 17, 2016: JAMA Cardiology
Kazuhiro Nishikawa, Tsunehiro Takahashi, Hiromasa Takaishi, Akira Miki, Hirokazu Noshiro, Takaki Yoshikawa, Yasunori Nishida, Satoru Iwasa, Hiroto Miwa, Toshiki Masuishi, Narikazu Boku, Yasuhide Yamada, Yasuhiro Kodera, Kazuhiro Yoshida, Satoshi Morita, Junichi Sakamoto, Shigetoyo Saji, Yuko Kitagawa
Paclitaxel is a standard second-line gastric cancer treatment in Japan. Trastuzumab could be active as second-line chemotherapy for taxane/trastuzumab-naïve patients with epidermal growth factor 2 (HER2)-positive advanced gastric cancer. Patients aged ≥20 years with HER2-positive, previously treated (except for trastuzumab and taxane), unresectable or recurrent gastric adenocarcinoma underwent combined trastuzumab (first and subsequent doses of 8 and 6 mg kg(-1) , respectively, every 3 weeks) and paclitaxel (days 1, 8, 15, every 4 weeks) treatment...
October 6, 2016: International Journal of Cancer. Journal International du Cancer
Charles Guenancia, Annick Lefebvre, Daniela Cardinale, Anthony F Yu, Sylvain Ladoire, François Ghiringhelli, Marianne Zeller, Luc Rochette, Yves Cottin, Catherine Vergely
PURPOSE: Patients with metabolic syndrome have a greater risk of cardiovascular disease, although their susceptibility to chemotherapy-induced cardiac disease is not well documented. The aim of this meta-analysis was to assess associations between obesity or being overweight and cardiotoxicity from anthracyclines and sequential anthracyclines and trastuzumab in patients with breast cancer. METHODS: We performed a random-effects analysis and a network meta-analysis and assessed publication bias...
September 10, 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
Francesca De Iuliis, Gerardo Salerno, Raffaella Corvino, Debora D'Aniello, Katia Cefalì, Ludovica Taglieri, Rosina Lanza, Susanna Scarpa
PURPOSE: Neoadjuvant chemotherapy (NCT) is a standard of care for locally advanced and initially inoperable breast cancer. NCT can test chemotherapy efficacy and can be followed by breast-conserving surgery. Considering taxanes as one of the most effective agents, we analyzed the efficacy of a neoadjuvant schedule without anthracyclines and based only on taxanes and carboplatin, trying to avoid cardiotoxicity, which is the most serious side effect correlated with anthracyclines. PATIENTS AND METHODS: We enrolled 61 patients with breast cancer, belonging to 4 subgroups, according to molecular phenotypes: 24 triple-negative/basal-like, 13 HER2-like, 20 luminal B, and 4 luminal A...
June 25, 2016: Clinical Breast Cancer
Ibrahim Fanous, Patrick Dillon
Cancer therapies, especially anthracyclines and monoclonal antibodies, have been linked with increased rates of cardiotoxicity. The development of some cardiac side effects happens over several months, and changes in ejection fraction can be detected long before permanent damage or disability occurs. Advanced heart failure could be averted with better and earlier detection. Methodologies for early detection of cardiac changes include stress echocardiograms, cardiac velocity measurements, radionuclide imaging, cardiac MRI and several potential biomarkers...
August 2016: Medical Oncology
Annelies H Boekhout, Jourik A Gietema, Bojana Milojkovic Kerklaan, Erik D van Werkhoven, Renske Altena, Aafke Honkoop, Maartje Los, Willem M Smit, Peter Nieboer, Carolien H Smorenburg, Caroline M P W Mandigers, Agnes J van der Wouw, Lonneke Kessels, Annette W G van der Velden, Petronella B Ottevanger, Tineke Smilde, Jaap de Boer, Dirk J van Veldhuisen, Ido P Kema, Elisabeth G E de Vries, Jan H M Schellens
IMPORTANCE: This is the first randomized placebo-controlled evaluation of a medical intervention for the prevention of trastuzumab-related cardiotoxic effects. OBJECTIVE: To determine as the primary end point whether angiotensin II antagonist treatment with candesartan can prevent or ameliorate trastuzumab-related cardiotoxic effects, defined as a decline in left ventricular ejection fraction (LVEF) of more than 15% or a decrease below the absolute value 45%. DESIGN: This randomized, placebo-controlled clinical study was conducted between October 2007 and October 2011 in 19 hospitals in the Netherlands, enrolling 210 women with early breast cancer testing positive for human epidermal growth factor receptor 2 (HER2) who were being considered for adjuvant systemic treatment with anthracycline-containing chemotherapy followed by trastuzumab...
August 1, 2016: JAMA Oncology
A Dias, W Claudino, R Sinha, C A Perez, D Jain
The Human Epidermal growth factor Receptor 2 (HER2) is a potent mediator of cellular growth and proliferation. It plays an important role in cardiac development and maintaining the physiologic function of an adult heart. Amplification of the HER2 gene, and the corresponding overexpression of the HER2 receptor, occurs in roughly 20% of breast tumors and is associated with a poor outcome. Molecular targeting of the HER2 receptor with the humanized monoclonal antibody, Trastuzumab has improved disease-free and overall survival in patients with both metastatic and early HER2-positive breast cancer...
August 2016: Critical Reviews in Oncology/hematology
Yasmin Hamirani, Ibrahim Fanous, Christopher M Kramer, Andrew Wong, Michael Salerno, Patrick Dillon
Some chemotherapeutic agents cause cardiotoxic effects including reduction in left ventricular ejection fraction (LVEF) and occasionally congestive heart failure. Anthracyclines and HER2 monoclonal antibodies are common offenders, but clinical practice data on LVEF changes, risk factors and acute recovery is lacking. We retrospectively examined the electronic medical record at an academic medical center for receipt of anthracyclines and/or trastuzumab from 2000 to 2013 in cancer patients. Patient characteristics and serial LVEF assessments were collected...
July 2016: Medical Oncology
Hsu-Chih Chien, Yea-Huei Kao Yang, Jane P F Bai
Importance: Trastuzumab is an essential medicine per the World Health Organization Model List, but its cardiac safety information in Asian women is limited. Objective: To estimate the rate and the risk of heart failure (HF) and/or cardiomyopathy (CM) in Asian women undergoing trastuzumab treatment. Design: This cohort study used the Taiwanese National Health Insurance Research Database (NHIRD), a nationwide claim database covering more than 99% of the entire Taiwanese population, to identify 23 006 women with incident breast cancer (BC) who received chemotherapy from 2006 to 2009...
June 16, 2016: JAMA Oncology
Christine C Davis, Amelia Zelnak, J William Eley, Daniel A Goldstein, Jeffrey M Switchenko, Trevor McKibbin
BACKGROUND: Trastuzumab targets the human epidermal growth factor receptor-2 (HER2). Cardiotoxicity is a potential adverse effect, manifesting as either an asymptomatic decline in left-ventricular ejection fraction or infrequently as largely reversible symptomatic heart failure (HF). Monitoring recommendations differ between product labeling and 2012 guidelines, and the clinical utility of serial cardiac monitoring in patients with metastatic breast cancer remains controversial. OBJECTIVE: The objectives of this study were to describe the frequency of monitoring, incidence of symptomatic or asymptomatic HF, overall effect on treatment, and cost of monitoring for cardiotoxicity...
September 2016: Annals of Pharmacotherapy
Erika Matos, Borut Jug, Rok Blagus, Branko Zakotnik
BACKGROUND: Cardiotoxicity is an important side effect of trastuzumab therapy and cardiac surveillance is recommended. OBJECTIVES: The aim of our study was to prospectively assess baseline patients' characteristics, level of N-terminal pro-brain natriuretic peptide (NT-proBNP) and echocardiographic parameters as possible predictors of trastuzumab-related cardiac dysfunction. METHODS: In a prospective cohort study, clinical, echocardiographic and neurohumoral assessment was performed at baseline, after 4, 8 and 12 months in breast cancer patients undergoing post-anthracycline (3-4 cycles) adjuvant therapy with trastuzumab...
July 2016: Arquivos Brasileiros de Cardiologia
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