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Trastuzumab cardiotoxicity

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https://www.readbyqxmd.com/read/29752560/anthracycline-use-for-early-stage-breast-cancer-in-the-modern-era-a-review
#1
REVIEW
Sakshi Jasra, Jesus Anampa
Anthracycline-based regimens have been an important treatment component for patients with breast cancer. As demonstrated in the last Early Breast Cancer Trialists' Collaborative Group (EBCTCG) meta-analysis, anthracycline-based regimens decrease breast cancer mortality by 20-30%. Anthracycline toxicities include the rare-but potential morbid-cardiotoxicity or leukemogenic effect, and the almost universal-but very distressing-alopecia. Due to potential toxicities, and large number of patients being exposed, several worldwide trials have re-examined the role of anthracycline-based regimens in the management of breast cancer...
May 11, 2018: Current Treatment Options in Oncology
https://www.readbyqxmd.com/read/29743983/chemotherapeutic-drugs-and-mitochondrial-dysfunction-focus-on-doxorubicin-trastuzumab-and-sunitinib
#2
REVIEW
Stefania Gorini, Antonella De Angelis, Liberato Berrino, Natalia Malara, Giuseppe Rosano, Elisabetta Ferraro
Many cancer therapies produce toxic side effects whose molecular mechanisms await full elucidation. The most feared and studied side effect of chemotherapeutic drugs is cardiotoxicity. Also, skeletal muscle physiology impairment has been recorded after many chemotherapeutical treatments. However, only doxorubicin has been extensively studied for its side effects on skeletal muscle. Chemotherapeutic-induced adverse side effects are, in many cases, mediated by mitochondrial damage. In particular, trastuzumab and sunitinib toxicity is mainly associated with mitochondria impairment and is mostly reversible...
2018: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/29719406/cardiotoxic-effects-of-the-novel-approved-anti-erbb2-agents-and-reverse-cardioprotective-effects-of-ranolazine
#3
Claudia De Lorenzo, Rolando Paciello, Gennaro Riccio, Domenica Rea, Antonio Barbieri, Carmela Coppola, Nicola Maurea
Purpose: Pertuzumab, a novel anti-epidermal growth factor receptor 2 humanized monoclonal antibody, and trastuzumab-emtansine (TDM1), a novel antibody-drug conjugate made up of trastuzumab covalently linked to the highly potent microtubule inhibitory agent DM1, have been recently approved by the US Food and Drug Administration for increasing the efficiency and safety of breast cancer therapy with trastuzumab. We investigated for the first time the potential cardiotoxic effects of pertuzumab and TDM1, which are not yet fully elucidated, and we tested whether ranolazine could blunt their cardiotoxicity...
2018: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29687878/anthracycline-and-trastuzumab-induced-cardiotoxicity-in-breast-cancer
#4
M A Nicolazzi, A Carnicelli, M Fuorlo, A Scaldaferri, R Masetti, R Landolfi, A M R Favuzzi
OBJECTIVE: Breast cancer is the most common cancer among women. In the last twenty years early diagnosis, neoadjuvant and adjuvant systemic treatment that targeted to specific molecular targets have significantly reduced the mortality from breast cancer. However, the increase in survival has allowed to observe the cardiotoxic effects of anticancer therapy and increased mortality from cardiovascular causes, resulting in a large literature where experts try to identify the correct management of this critical problem...
April 2018: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/29621991/adjuvant-trastuzumab-duration-trials-in-her2-positive-breast-cancer-what-results-would-be-practice-changing-persephone-investigator-questionnaire-prior-to-primary-endpoint-results
#5
Louise Hiller, Janet A Dunn, Shrushma Loi, Anne-Laure Vallier, Donna L Howe, David A Cameron, David Miles, Andrew M Wardley, Helena M Earl
BACKGROUND: Twelve months treatment is the current standard of care for adjuvant trastuzumab in patients with HER2 positive early breast cancer however the optimal duration is not known. Persephone is a non-inferiority randomised controlled trial comparing 6- to 12-months of trastuzumab. In this trial there will be a trade-off between a possible small decrease in disease-free survival (DFS) with 6-months and reduced cardiotoxicity and cost. METHODS: A structured questionnaire asked clinicians who had recruited patients into the Persephone trial about their prior beliefs with regards to the clinical effectiveness of trastuzumab and cardiotoxicity profile, in the comparison of 6- and 12-month durations...
April 5, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29582557/five-year-results-of-a-phase-ii-trial-of-preoperative-5-fluorouracil-epirubicin-cyclophosphamide-followed-by-docetaxel-with-capecitabine-wtx-with-trastuzumab-in-her2-positive-patients-for-patients-with-stage-ii-or-iii-breast-cancer
#6
Frankie Ann Holmes, Beth A Hellerstedt, John E Pippen, Svetislava J Vukelja, Rufus P Collea, Darren M Kocs, Joanne L Blum, Kristi J McIntyre, Minal A Barve, Barry D Brooks, Cynthia R Osborne, Yunfei Wang, Lina Asmar, Joyce O'Shaughnessy
We aimed to increase pathologic complete response (pCR) in patients with invasive breast cancer by adding preoperative capecitabine to docetaxel following 5-fluorouracil, epirubicin, cyclophosphamide (FEC) (with trastuzumab for patients with HER2-positive disease) and to evaluate 5-year disease-free survival (DFS) associated with this preoperative regimen. Chemotherapy included four cycles of FEC100 (5-fluorouracil 500 mg/m2 , epirubicin 100 mg/m2 , cyclophosphamide 500 mg/m2 IV on Day 1 every 21 days) followed by 4 21-day cycles of docetaxel (35 mg/m2  days 1 and 8) concurrently with capecitabine (825 mg/m2 orally twice daily for 14 days followed by 7 days off) (wTX)...
March 26, 2018: Cancer Medicine
https://www.readbyqxmd.com/read/29569424/left-atrial-volume-in-patients-with-her2-positive-breast-cancer-one-step-further-to-predict-trastuzumab-related-cardiotoxicity
#7
Corinna Bergamini, Giulia Dolci, Andrea Rossi, Flavia Torelli, Luca Ghiselli, Laura Trevisani, Giulia Vinco, Stella Truong, Francesca La Russa, Giorgio Golia, Annamaria Molino, Giovanni Benfari, Flavio Luciano Ribichini
BACKGROUND: Trastuzumab (TZ) therapy requires careful monitoring of left ventricular (LV) ejection fraction (LVEF) because it can be potentially cardiotoxic. However, LVEF is an imperfect parameter and there is a need to find other variables to predict cardiac dysfunction early. Left atrium (LA) enlargement has proven to be a powerful predictor of adverse outcomes in several disease entities. HYPOTHESIS: Baseline LA volume enlargement might predict TZ-related LV dysfunction...
March 22, 2018: Clinical Cardiology
https://www.readbyqxmd.com/read/29561992/global-longitudinal-strain-accuracy-for-cardiotoxicity-prediction-in-a-cohort-of-breast-cancer-patients-during-anthracycline-and-or-trastuzumab-treatment
#8
Eliza de Almeida Gripp, Gabriela Escudini de Oliveira, Luiz Augusto Feijó, Marcelo Iorio Garcia, Sergio Salles Xavier, Andréa Silvestre de Sousa
BACKGROUND: The high cardiotoxicity morbidity and mortality rates associated with the antineoplastic therapy for breast cancer could be reduced with the early use of cardioprotective drugs. However, the low sensitivity of left ventricular ejection fraction limits its use in that preventive strategy. New parameters, such as global longitudinal strain, are being used in the early detection of contractile function changes. OBJECTIVES: To assess the incidence of cardiotoxicity in patients treated for breast cancer, the independent factors associated with that event, and the ability of strain to identify it early...
February 2018: Arquivos Brasileiros de Cardiologia
https://www.readbyqxmd.com/read/29557343/chemotherapy-related-cardiac-dysfunction-a-systematic-review-of-genetic-variants-modulating-individual-risk
#9
REVIEW
Marijke Linschoten, Arco J Teske, Maarten J Cramer, Elsken van der Wall, Folkert W Asselbergs
Chemotherapy-related cardiac dysfunction is a significant side effect of anticancer treatment. Risk stratification is based on clinical- and treatment-related risk factors that do not adequately explain individual susceptibility. The addition of genetic variants may improve risk assessment. We conducted a systematic literature search in PubMed and Embase, to identify studies investigating genetic risk factors for chemotherapy-related cardiac dysfunction. Included were articles describing genetic variants in humans altering susceptibility to chemotherapy-related cardiac dysfunction...
January 2018: Circulation. Genomic and precision medicine
https://www.readbyqxmd.com/read/29536232/development-and-evaluation-of-tri-functional-immunoliposomes-for-the-treatment-of-her2-positive-breast-cancer
#10
Tanaya Vaidya, Robert M Straubinger, Sihem Ait-Oudhia
PURPOSE: Trastuzumab combined with Doxorubicin (DOX) demonstrates significant clinical activity in human epidermal growth factor receptor-2 (HER2)-positive breast cancer (BC). However, emergence of treatment resistance and trastuzumab associated cardiotoxicity remain clinical challenges. In an effort to improve patient outcome, we have developed and evaluated novel tri-functional immunoliposomes (TFIL) that target HER2-receptors on BC cells and CD3-receptors on T-lymphocytes, and deliver DOX...
March 13, 2018: Pharmaceutical Research
https://www.readbyqxmd.com/read/29497813/a-novel-way-to-manage-trastuzumab-cardiotoxicity
#11
Diaddin Hamdan, François Darrouzain, Theodora Bejan-Angoulvant, Charles Isorni, Laurent Zelek, Gilles Paintaud, Anne Janin, Guilhem Bousquet
PURPOSE: Trastuzumab is the most widely prescribed anti-HER2 humanized monoclonal antibody. Cardiac toxicity is the only limiting toxicity of trastuzumab and it is of particular concern in patients with complete response, since the drug needs to be stopped, with a risk of disease relapse. To date, no pharmacological data on trastuzumab cardiotoxicity in patients have been made available. Here, we provide proof of concept, demonstrating that it was possible to prevent trastuzumab-induced cardiotoxicity by modifying the drug administration schedule...
April 2018: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/29467663/ranolazine-attenuates-trastuzumab-induced-heart-dysfunction-by-modulating-ros-production
#12
Gennaro Riccio, Salvatore Antonucci, Carmela Coppola, Chiara D'Avino, Giovanna Piscopo, Danilo Fiore, Carlo Maurea, Michele Russo, Domenica Rea, Claudio Arra, Gerolama Condorelli, Fabio Di Lisa, Carlo G Tocchetti, Claudia De Lorenzo, Nicola Maurea
The ErbB2 blocker trastuzumab improves survival in oncologic patients, but can cause cardiotoxicity. The late Na+ current inhibitor ranolazine has been shown to counter experimental HF, including doxorubicin cardiotoxicity (a condition characterized by derangements in redox balance), by lowering the levels of reactive oxygen species (ROS). Since ErbB2 can modulate ROS signaling, we tested whether trastuzumab cardiotoxicity could be blunted by ranolazine via redox-mediated mechanisms. Trastuzumab decreased fractional shortening and ejection fraction in mice, but ranolazine prevented heart dysfunction when co-administered with trastuzumab...
2018: Frontiers in Physiology
https://www.readbyqxmd.com/read/29465031/-management-of-cardiovascular-complications-secondary-to-medical-treatment-of-cancer
#13
Ann Banke, Anne Polk, Dorte Nielsen, Lars Videbæk, Ulrik Overgaard, Emil Loldrup Fosbøl, Merete Vaage-Nielsen, Kirsten Melgaard Nielsen, Morten Schou
As the prognoses of both heart and cancer patients have improved along with a longer life expectancy in the general population, the prevalence of both heart- and cancer diseases is increasing. Thus, a larger proportion of cancer patients will have cardiovascular co-morbidity and an increased risk of cardiovascular complications during and after cancer treatment. In this article, the current knowledge on the prevention, monitoring and treatment of cardiotoxicity induced by medical anti-cancer treatment with focus on anthracyclines, trastuzumab and 5-fluorouracil is described...
February 12, 2018: Ugeskrift for Laeger
https://www.readbyqxmd.com/read/29464058/type-iib-dna-topoisomerase-is-downregulated-by-trastuzumab-and-doxorubicin-to-synergize-cardiotoxicity
#14
Jiangsong Jiang, Nishant Mohan, Yukinori Endo, Yi Shen, Wen Jin Wu
Despite heightened risk of cardiotoxicity associated with combination therapy of anthracyclines and trastuzumab in HER2-positive breast cancer patients, little research effort has been invested in exploring the molecular mechanisms of cardiotoxicity induced by this combination therapy. In this study, we demonstrate that trastuzumab downregulates both gene and protein expressions of type IIB DNA topoisomerase/DNA topoisomerase IIB (TOP2B), a major intracellular target mediating doxorubicin-induced cardiotoxicity, in human primary cardiomyocytes...
January 19, 2018: Oncotarget
https://www.readbyqxmd.com/read/29454478/usefulness-of-integrating-heart-failure-risk-factors-into-impairment-of-global-longitudinal-strain-to-predict-anthracycline-related-cardiac-dysfunction
#15
M Wesley Milks, Michael R Velez, Nishaki Mehta, Abiodun Ishola, Thomas Van Houten, Vedat O Yildiz, Raquel Reinbolt, Maryam Lustberg, Sakima A Smith, David A Orsinelli
The prediction of cancer therapeutics-related cardiac dysfunction (CTRCD) is an essential aspect of care for individuals who receive potentially cardiotoxic oncologic treatments. Certain clinical risk factors have been described for incident CTRCD, and measurement of left ventricular (LV) longitudinal strain by speckle tracking 2-dimensional echocardiography (2DE) is the best-validated myocardial mechanical imaging assessment to detect subtle changes in LV function during cancer treatment. However, the direct integration of clinical and imaging risk factors to predict CTRCD has not yet been extensively examined...
April 1, 2018: American Journal of Cardiology
https://www.readbyqxmd.com/read/29429038/pharmacodynamic-modeling-of-cardiac-biomarkers-in-breast-cancer-patients-treated-with-anthracycline-and-trastuzumab-regimens
#16
Aurelia H M de Vries Schultink, Annelies H Boekhout, Jourik A Gietema, Artur M Burylo, Thomas P C Dorlo, J G Coen van Hasselt, Jan H M Schellens, Alwin D R Huitema
Trastuzumab is associated with cardiotoxicity, manifesting as a decrease of the left-ventricular ejection fraction (LVEF). Administration of anthracyclines prior to trastuzumab increases risk of cardiotoxicity. High-sensitive troponin T and N-terminal-pro-brain natriuretic peptide (NT-proBNP) are molecular markers that may allow earlier detection of drug-induced cardiotoxicity. In this analysis we aimed to quantify the kinetics and exposure-response relationships of LVEF, troponin T and NT-proBNP measurements, in patients receiving anthracycline and trastuzumab...
February 10, 2018: Journal of Pharmacokinetics and Pharmacodynamics
https://www.readbyqxmd.com/read/29381193/racial-disparities-in-the-rate-of-cardiotoxicity-of-her2-targeted-therapies-among-women-with-early-breast-cancer
#17
Anya Litvak, Bhavina Batukbhai, Stuart D Russell, Hua-Ling Tsai, Gary L Rosner, Stacie C Jeter, Deborah Armstrong, Leisha A Emens, John Fetting, Antonio C Wolff, Raquel Silhy, Vered Stearns, Roisin M Connolly
BACKGROUND: Human epidermal growth factor receptor 2 (HER2)-targeted therapies are highly effective at preventing breast cancer recurrence but are associated with cardiotoxicity in some patients, and minimal data are available regarding racial disparities in the incidence of this toxicity. The authors conducted a retrospective study to analyze the association of black or white race with treatment-induced cardiotoxicity and incomplete therapy among patients with HER2-positive early breast cancer...
May 1, 2018: Cancer
https://www.readbyqxmd.com/read/29374719/phase-ii-study-of-s-1-plus-trastuzumab-for-her2-positive-metastatic-breast-cancer-gbccsg-01
#18
MULTICENTER STUDY
Takaaki Fujii, Jun Horiguchi, Yasuhiro Yanagita, Yukio Koibuchi, Fumihiro Ikeda, Nobuyuki Uchida, Morihiko Kimura
AIM: Treatment strategies for patients with human epidermal growth factor 2 (HER2)-positive metastatic breast cancer (MBC) have significantly progressed. The use of trastuzumab, a monoclonal antibody targeting the HER2 (human epidermal growth factor 2) protein, in combination with chemotherapy improves survival in patients with HER2-positive breast cancer. S-1, an oral combination of fluorouracil derivatives, is widely used in Japan and is more convenient than intravenous drugs. However, little is known about the combination of S-1 and trastuzumab in patients with HER2-positive MBC...
February 2018: Anticancer Research
https://www.readbyqxmd.com/read/29361617/-cardiotoxicity-of-cancer-chemotherapy-mechanisms-and-therapeutic-approach
#19
Hiroshi Akazawa
Recent progress in cancer chemotherapy has improved the long-term outcome for cancer patients. Under such circumstances, it is increasingly of clinical importance to manage the cardiovascular complications, which are related to both cancer itself and adverse effects of cancer therapies. Among the most concerning as cardiovascular complications of cancer therapies is chemotherapy-induced cardiotoxicity or chemotherapy-related cardiac dysfunction(CTRCD). CTRCD has been intuitively classified according to the extent of structural abnormalities and degree of reversibility; type 1 is irreversible and dose-dependent with structural abnormalities, and type 2 is reversible after cessation of treatment and dose-independent without structural abnormalities...
December 2017: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/29305325/modeling-trastuzumab-related-cardiotoxicity-in-vitro-using-human-stem-cell-derived-cardiomyocytes
#20
Yosuke K Kurokawa, Michael R Shang, Rose T Yin, Steven C George
Trastuzumab (Herceptin® ), a monoclonal antibody against the ErbB2 (HER2) receptor, has significantly improved clinical outcomes for HER2+ breast cancer patients. However, the drug also has known cardiotoxic side effects through mechanisms that are not fully understood. Here we utilized human induced pluripotent stem cell-derived cardiomyocytes (iPS-CMs) to model trastuzumab-related cardiotoxicity in vitro. We demonstrate that cardiotoxic effects of ErbB2 inhibition by trastuzumab can be recapitulated only when the cardioprotective effects of ErbB2/4 signaling is observed...
March 15, 2018: Toxicology Letters
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