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Heart herceptin

Volkmar Müller, Michael Clemens, Jacek Jassem, Nedal Al-Sakaff, Petra Auclair, Eveline Nüesch, Debbie Holloway, Mona Shing, Yung-Jue Bang
BACKGROUND: Trastuzumab (Herceptin® [H]) is the standard of care for HER2-positive locally advanced/metastatic breast cancer and gastric/gastroesophageal junction (GEJ) cancer. However, there is a paucity of data available on long-term H treatment of patients. The Rollover Protocol (ROP) Study was conducted to report safety data for patients with HER2-positive locally advanced/metastatic breast and gastric/GEJ cancer who have received long-term H therapy (≥ 5 years and ≥ 3 years for breast and gastric/GEJ cancer, respectively)...
March 15, 2018: BMC Cancer
J Gligorov, B Ataseven, M Verrill, M De Laurentiis, K H Jung, H A Azim, N Al-Sakaff, S Lauer, M Shing, X Pivot
AIM: To assess the safety and tolerability of adjuvant subcutaneous trastuzumab (Herceptin® SC, H SC), delivered from an H SC Vial via hand-held syringe (Cohort A) or single-use injection device (Cohort B), with or without chemotherapy, for human epidermal growth factor receptor 2 (HER2)-positive stage I to IIIC early breast cancer (EBC) in the phase III SafeHer study (NCT01566721). METHODS: Patients received 600 mg fixed-dose H SC every 3 weeks for 18 cycles...
September 2017: European Journal of Cancer
Dimitrios Zardavas, Thomas M Suter, Dirk J Van Veldhuisen, Jutta Steinseifer, Johannes Noe, Sabine Lauer, Nedal Al-Sakaff, Martine J Piccart-Gebhart, Evandro de Azambuja
Purpose Women receiving trastuzumab with chemotherapy are at risk for trastuzumab-related cardiac dysfunction (TRCD). We explored the prognostic value of cardiac markers (troponins I and T, N-terminal prohormone of brain natriuretic peptide [NT-proBNP]) to predict baseline susceptibility to develop TRCD. We examined whether development of cardiac end points or significant left ventricular ejection fraction (LVEF) drop was associated with markers' increases. Patients and Methods Cardiac marker assessments were coupled with LVEF measurements at different time points for 533 patients from the Herceptin Adjuvant (HERA) study who agreed to participate in this study...
March 10, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
Zeeshan Jawa, Ruth M Perez, Lydia Garlie, Maharaj Singh, Rubina Qamar, Bijoy K Khandheria, Arshad Jahangir, Yang Shi
BACKGROUND: Trastuzumab targets the human epidermal growth factor receptor 2 oncogene and in combination with first-line therapy results in significantly improved survival outcomes and has thus become standard of care in both adjuvant and metastatic settings. While it is estimated that 1% to 4% of patients treated with trastuzumab will develop heart failure and ∼10% will experience a reduction in left ventricular ejection fraction (LVEF), the patient risk factors associated with trastuzumab-induced cardiotoxicity (TIC) are unclear...
November 2016: Medicine (Baltimore)
Emma L Wilkinson, James E Sidaway, Michael J Cross
Cardiotoxicity induced by anti-cancer therapeutics is a severe, and potentially fatal, adverse reaction of the heart in response to certain drugs. Current in vitro approaches to assess cardiotoxicity have focused on analysing cardiomyocytes. More recently it has become apparent that non-cardiomyocyte cells of the heart can potentially contribute to cardiotoxicity. Herceptin and doxorubicin are known to induce cardiotoxicity in the clinic. The effect of these drugs on the endothelial tight junction barrier was tested by analysing tight junction formation and zona occludens-1 (ZO-1) levels, revealing that Herceptin and doxorubicin are able to induce barrier perturbment and decrease barrier function in human cardiac microvascular endothelial cells (HCMECs) leading to increased permeability...
October 15, 2016: Biology Open
Shanly C Seferina, Maaike de Boer, M Wouter Derksen, Franchette van den Berkmortel, Roel J W van Kampen, Agnès J van de Wouw, Manuela Joore, Petronella G M Peer, Adri C Voogd, Vivianne C G Tjan-Heijnen
INTRODUCTION: We assessed the incidence and timing of first cardiac events, impact on trastuzumab prescription, and role of left ventricular ejection fraction (LVEF) monitoring in daily practice of trastuzumab-treated patients with human epidermal growth receptor 2 (HER2)-positive early breast cancer. METHODS: We included all patients with stage I-III breast cancer diagnosed in the early years (2005-2007) after the introduction of adjuvant trastuzumab in five hospitals in Southeast Netherlands...
May 2016: Oncologist
Sheng Zhang, Tingting Meng, Jingjing Liu, Xiaobei Zhang, Jin Zhang
Cardiotoxicity is a well-recognized side effect induced by chemotherapeutic drugs such as anthracycline and trastuzumab through different mechanisms. Currently, accumulating evidence supports that dexrazoxane (DZR) can minimize the risk of cardiotoxicity. In this study, we investigated whether dexrzoxane could reduce cardiotoxicity in the treatment of anthracycline combined with trastuzumab. We randomly divided 90 experimental F344 rats into control group, chemotherapeutics and trastuzumab (doxorubicin [DOX] + herceptin [Her]) group, and chemotherapeutics, trastuzumab, and DZR (DOX + Her + DZR) group...
January 2015: Medicine (Baltimore)
Karen Lam, Conrad Chan, Susan J Done, Mark N Levine, Raymond M Reilly
INTRODUCTION: (111)In-BzDTPA-pertuzumab is a novel imaging probe for detecting changes in HER2 expression in breast cancer (BC) caused by treatment with trastuzumab (Herceptin). Our aim was to evaluate the pharmacokinetics, normal tissue biodistribution, radiation dosimetry and acute toxicity of (111)In-BzDTPA-pertuzumab in non-tumor bearing mice in order to obtain regulatory approval to advance this agent to a first-in-humans Phase I/II clinical trial. METHODS: Biodistribution and pharmacokinetic studies were performed in non-tumor bearing Balb/c mice injected i...
February 2015: Nuclear Medicine and Biology
Evandro de Azambuja, Marion J Procter, Dirk J van Veldhuisen, Dominique Agbor-Tarh, Otto Metzger-Filho, Jutta Steinseifer, Michael Untch, Ian E Smith, Luca Gianni, Jose Baselga, Christian Jackisch, David A Cameron, Richard Bell, Brian Leyland-Jones, Mitch Dowsett, Richard D Gelber, Martine J Piccart-Gebhart, Thomas M Suter
PURPOSE: To document the rate and outcome of trastuzumab-associated cardiac dysfunction in patients following 1 or 2 years of adjuvant therapy. PATIENTS AND METHODS: The Herceptin Adjuvant (HERA) trial is a three-arm, randomized trial comparing 2 years or 1 year of trastuzumab with observation in 5,102 patients with human epidermal growth factor receptor 2 (HER2) -positive early-stage breast cancer. Cardiac function was closely monitored. Eligible patients had left ventricular ejection fraction (LVEF) ≥ 55% at study entry following neoadjuvant chemotherapy with or without radiotherapy...
July 10, 2014: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
Tania Babar, Christopher Blomberg, Eileen Hoffner, Xinhua Yan
A significant milestone in the treatment of breast cancer is the identification of the HER2 receptor as a drug target for cancer therapies. Trastuzumab (Herceptin), a monoclonal antibody that blocks the HER2 receptor, is among the first of such drugs approved by the US Food and Drug Administration for targeted cancer therapy. Clinical studies have shown that Trastuzumab significantly improves the overall survival of breast cancer patients. However, an unforeseen significant side-effect of cardiotoxicity manifested as left ventricular dysfunction and heart failure...
2014: Current Pharmaceutical Design
H-T Tsai, C Isaacs, A Z Fu, J L Warren, A N Freedman, A Barac, C-Y Huang, A L Potosky
Randomized controlled trials have reported a 4-5 times increased risk of heart failure (HF) in breast cancer patients receiving trastuzumab (Herceptin (®) ) compared to patients who do not receive trastuzumab. However, data regarding the cardiac effects of trastuzumab on elderly patients treated in general practice remain very limited. Using the US surveillance, epidemiology, and end results (SEER)-Medicare database, we conducted a retrospective cohort study on the cardiac effects of trastuzumab use in all incident breast cancer patients diagnosed from 1998 to 2007 who were 66 years and older, had no prior recent claims for cardiomyopathy (CM) or HF, and were followed through 2009...
February 2014: Breast Cancer Research and Treatment
I Láng, R Bell, F Y Feng, R I Lopez, J Jassem, V Semiglazov, N Al-Sakaff, D Heinzmann, J Chang
AIMS: Trastuzumab, in combination with chemotherapy, is the standard of care for patients with early and metastatic human epidermal growth factor receptor 2 (HER2)-positive breast cancer. The Retreatment after HErceptin Adjuvant trial assessed the efficacy and safety of trastuzumab plus a taxane as first-line treatment for patients with metastatic breast cancer (MBC) who had relapsed after adjuvant trastuzumab for HER2-positive early breast cancer. MATERIALS AND METHODS: In total, 43 patients with HER2-positive MBC who had received previous adjuvant trastuzumab for ≥10 months, with a relapse-free interval of ≥6 months after the last adjuvant trastuzumab dose, were recruited...
February 2014: Clinical Oncology: a Journal of the Royal College of Radiologists
Christine Y Lu, Preeyaporn Srasuebkul, Anna K Drew, Katie Chen, Robyn L Ward, Sallie-Anne Pearson
PURPOSE: To manage the potential trastuzumab mediated cardiotoxicity, clinical guidelines recommend pre-treatment cardiac function assessment and 3-monthly reassessment during therapy. This study examined rates of cardiac function assessment and predictors of assessment among patients receiving trastuzumab for HER2+ metastatic breast cancer treatment in routine clinical care. METHODS: Our cohort comprised 3418 women receiving trastuzumab for HER2+ metastatic breast cancer under Australia's nationally funded Herceptin Program (2001-2010)...
August 2013: Breast: Official Journal of the European Society of Mastology
M Untch
No abstract text is available yet for this article.
December 2002: Onkologie
Carmine Fedele, Gennaro Riccio, Angela Eliana Malara, Giuseppe D'Alessio, Claudia De Lorenzo
The ErbB2 receptor is a proto-oncogene associated with a poor prognosis in breast cancer. Herceptin, the only humanized anti-ErbB2 antibody currently in clinical use, has proven to be an essential tool in the immunotherapy of breast carcinoma, but induces cardiotoxicity. ErbB2 is involved in the growth and survival pathway of adult cardiomyocytes; however, its levels in the adult heart are much lower than those found in breast cancer cells, the intended targets of anti-ErbB2 antibodies. Furthermore, clinical trials have shown relatively low cardiotoxicity for Lapatinib, a dual kinase inhibitor of EGFR and ErbB2, and Pertuzumab, a new anti-ErbB2 monoclonal antibody currently in clinical trials, which recognizes an epitope distant from that of Herceptin...
July 2012: Breast Cancer Research and Treatment
Ronny S Jiji, Christopher M Kramer, Michael Salerno
Cardiotoxicity due to administration of cancer therapeutic agents such as anthracyclines and herceptin are well described. Established guidelines to screen for chemotherapy-related cardiotoxicity (CRC) are primarily based on serial assessment of left ventricular (LV) ejection fraction (EF). However, other parameters such as LV volume, diastolic function, and strain may also be useful in screening for cardiotoxicity. More recent advances in molecular imaging of apoptosis and tissue characterization by cardiac MRI are techniques which might allow early detection of patients at high risk for developing cardiotoxicity prior to a drop in EF...
April 2012: Journal of Nuclear Cardiology: Official Publication of the American Society of Nuclear Cardiology
Stefan A Lange, Bernd Ebner, Astrid Wess, Matthias Kögel, Mieczyslaw Gajda, Thomas Hitschold, Jens Jung
OBJECTIVE: Recent studies in breast cancer patients and Trastuzumab therapy (Herceptin) showed a development of a toxic cardiomyopathy as a severe complication. The aim of this study was to discover early changes in cardiac function and morphology. METHODS: We studied 42 female patients with Her-2/-neu over-expression in breast cancer by echocardiography before, 3, and 6 months after start of the adjuvant Herceptin therapy. All values were mean value ± standard deviation...
June 2012: Clinical Research in Cardiology: Official Journal of the German Cardiac Society
Jan Hysing, Erik Wist
BACKGROUND: Breast cancer with overexpression of the HER2 receptor is an aggressive type of breast cancer with poor prognosis. Trastuzumab (Herceptin) is a monoclonal antibody that binds to the HER2 receptor on the cell surface blocking the signals that promote cell-growth proliferation. Trastuzumab treatment has almost halved the risk of relapse, when given as an adjuvant, and has improved the overall survival in metastatic breast cancer. However, when given alone or in combination with cardiotoxic chemotherapy, especially anthracyclines, trastuzumab may lead to congestive heart failure of varying severity...
November 15, 2011: Tidsskrift for Den Norske Lægeforening: Tidsskrift for Praktisk Medicin, Ny Række
Nasser Ghaly Yousif, Fadhil G Al-Amran
BACKGROUND: Cardiac inflammation and generation of oxidative stress are known to contribute to trastuzumab (herceptin) induced cardiac toxicity. Toll-like receptors (TLRs) are a part of the innate immune system and are involved in cardiac stress reactions. Since TLR4 might play a relevant role in cardiac inflammatory signaling, we investigated whether or not TLR4 is involved in trastuzumab induced cardiotoxicity. METHODS: Seven days after a single injection of herceptin (2 mg/kg; i...
October 14, 2011: BMC Cardiovascular Disorders
Krishna K Singh, Praphulla C Shukla, Adrian Quan, Fina Lovren, Yi Pan, Jesse I Wolfstadt, Milan Gupta, Mohammed Al-Omran, Howard Leong-Poi, Hwee Teoh, Subodh Verma
P53 protein levels are elevated by trastuzumab and the biologically similar rat ERBB2/HER2/NEU antibody; and that this coincides with enhanced apoptosis, increased cleaved caspase-3 levels and diminished cardiac function. We also demonstrate that MDM2 may be a regulatory target of anti-ERBB2 thereby implicating the MDM2/p53 axis as a potential molecular component for the undesirable cardiac outcomes noted with trastuzumab. Finally, we show that these MDM2/p53-mediated events are independent of both the ERK1/2 and Akt systems...
July 29, 2011: Biochemical and Biophysical Research Communications
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