Cardiovascular side effects of cancer therapies: a position statement from the Heart Failure Association of the European Society of Cardiology
ABSTRACT The reductions in mortality and morbidity being achieved among cancer patients with current therapies represent a major achievement. However, given their mechanisms of action, many anti-cancer agents may have significant potential for cardiovascular side effects, including the induction of heart failure. The magnitude of this problem remains unclear and is not readily apparent from current clinical trials of emerging targeted agents, which generally under-represent older patients and those with significant co-morbidities. The risk of adverse events may also increase when novel agents, which frequently modulate survival pathways, are used in combination with each other or with other conventional cytotoxic chemotherapeutics. The extent to which survival and growth pathways in the tumour cell (which we seek to inhibit) coincide with those in cardiovascular cells (which we seek to preserve) is an open question but one that will become ever more important with the development of new cancer therapies that target intracellular signalling pathways. It remains unclear whether potential cardiovascular problems can be predicted from analyses of such basic signalling mechanisms and what pre-clinical evaluation should be undertaken. The screening of patients, optimization of therapeutic schemes, monitoring of cardiovascular function during treatment, and the management of cardiovascular side effects are likely to become increasingly important in cancer patients. This paper summarizes the deliberations of a cross-disciplinary workshop organized by the Heart Failure Association of the European Society of Cardiology (held in Brussels in May 2009), which brought together clinicians working in cardiology and oncology and those involved in basic, translational, and pharmaceutical science.
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ABSTRACT: In recent years, a number of new molecules - commonly known as biological therapies - have been approved or are in late stages of regulatory evaluation for the treatment of advanced breast cancer. These innovative compounds have improved treatment efficacy and have probably contributed to the increase in survival length observed in some breast cancer subtypes. However, these agents are not deprived of toxicity, which can impair quality of life and may occasionally be life-threatening. In this article, we reviewed the most common toxicities associated with these drugs and provided a number of practical recommendations on their optimal clinical management.Breast (Edinburgh, Scotland) 10/2013; 22(6). DOI:10.1016/j.breast.2013.09.009 · 2.58 Impact Factor
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ABSTRACT: Anthracyclines remain the cornerstone of treatment in many malignancies but these agents have a cumulative dose relationship with cardiotoxicity. Development of cardiomyopathy and congestive heart failure induced by anthracyclines are typically dose-dependent, irreversible, and cumulative. Although past studies of cardiotoxicity have focused on anthracyclines, more recently interest has turned to anticancer drugs that target many proteins kinases, such as tyrosine kinases. An attractive model to explain the mechanism of this cardiotoxicity could be myocyte loss through cell death pathways. Inhibition of mitochondrial transition permeability is a valuable tool to prevent doxorubicin-induced cardiotoxicity. In response to anthracycline treatment, activation of several protein kinases, neuregulin/ErbB2 signaling, and transcriptional factors modify mitochondrial functions that determine cell death or survival through the modulation of mitochondrial membrane permeability. Cellular response to anthracyclines is also modulated by a myriad of transcriptional factors that influence cell fate. Several novel targeted chemotherapeutic agents have been associated with a small but worrying risk of left ventricular dysfunction. Agents such as trastuzumab and tyrosine kinase inhibitors can lead to cardiotoxicity that is fundamentally different from that caused by anthracyclines, whereas biological effects converge to the mitochondria as a critical target.03/2012; 2012:951539. DOI:10.1155/2012/951539
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ABSTRACT: Die vorliegende Arbeit befaßt sich mit der Entwicklung und der Anwendung einer präparativen HPLC-Methode zur Trennung von Phosphoniumsalzen. Es werden analytische Chromatogramme vorgestellt, die die Anwendbarkeit von Ionen-Paar- und Adsorptions-Chromatographie nachweisen. Letztere wurde sowohl in Anwesenheit als auch in Abwesenheit überschüssiger Säuren durchgeführt. Die Methode wurde zur Trennung von Phosphoniumsalzen im präparativen Maßstab weiter optimiert. Die Identifizierung der einzelnen chromatographischen Fraktionen geschah mit Hilfe der 1H- und 31P-NMR-Spektroskopie.Fresenius Zeitschrift für Analytische Chemie 01/1981; 305(5):347-354. DOI:10.1007/BF00483195