Medizinische Fachliteratur zur Herzschädigung durch Chemo- und Strahlentherapie bei Brustkrebs (Teil 2)
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heart failure chemotherapeutic agents breast cancer
cardiooncology chemotherapeutic breast cancer
und zusammengestellt
von Dr. Joachim Gruber
Annals of Oncology 23 (Supplement 7): vii155-vii166, 2012
doi:10.1093/annonc/mds293
G. Curigliano1, D. Cardinale, T. Suter, G. Plataniotis, E. de Azambuja, M. T. Sandri, C. Criscitiello, A. Goldhirsch, C. Cipolla & F. Roila,
on behalf of the ESMO Guidelines Working Group*
*Correspondence to: European Society for Medical Oncology (ESMO) Guidelines Working Group, ESMO Head Office, Via L. CH-6962 Viganello-Lugano, Switzerland; E-mail: clinicalguidelines@esmo.org
Approved by the ESMO Guidelines Working Group: February 2010, last update July 2012.
This publication supersedes the previously published version- -Ann Oncol 2010; 21(Suppl 5):v277-v282
These guidelines summarize the deliberations of a cross-disciplinary working group
Zusammenfassung Das Risiko für Kardiotoxizität wächst mit der kumulativen [also insgesamt eingenommenen] Dosis. Studien, welche die kumulative Wahrscheinlichkeit von doxorubizin-induzierte Herzinsufizienz ausgewertet haben, fanden folgende Raten
Die empfohlene maximale kumulative Lebenszeitdosis für Doxorubizin ist 400 - 550 mg/m2 Körperoberfläche.
Diagramm (in cache), das die Körperoberfläche aus Gewicht und Größe bestimmen lässt. Für 1.6 m2 Körperoberfläche (mittlerer Wert für Frauen) ergeben sich damit folgende Dosen
Nach der Behandlung mit Anthrazyklinen ist es wichtig, die Herzfunktion aller Patienten erneut auszuwerten, um asymptomatische (symptomlose) Patienten mit erhöhter Herzschädigung zu identifizieren.
Die gemessenen LVEF-Werte variieren beträchtlich, weil Krebsmedikament-unabhängige Faktoren wesentlichen Einfluss auf die Herzfunktionen haben können. ... die LVEF-Messung ist ein relativ unempfindliches Werkzeug zum Entdecken von Kardiotoxizität im Frühstadium. Das kommt weitgehend daher, dass keine nennenswerte LVEF-Änderung auftritt, bis ein kritischer Betrag an Herzmuskelschädigung stattgefunden hat, und sie erst dann in den Vordergrund tritt, nachdem Ausgleichsmechanismen erschöpft sind. Darüberhinaus bereitet eine LVEF-Messung eine Anzahl von Herausforderungen, was die Bildqualität, die Annahme der linksventrikulären Geometrie, Abhängigkeit von der Belastung und [Facharzt-]Expertise angeht. Tabelle 3: Kardiovaskuläre Beobachtung während und nach Krebstherapie with potentiell nicht-reversibler (Typ I) oder reversibler (Typ II) Kardiotoxizität
Zeichenerklärung Quelle: Evidence Based Health Care -- Practice guidelines levels of evidence and grades of recommendations used by the National Guideline Clearinghouse (cached)
Behandlung von Trastuzumab-Kardiotoxizität Behandlung von Kardiotoxizität durch Trastuzumab hat zwei unterschiedliche Aspekte:
Symptomatischer linksventriklärer Dysfunktion muss mit Herzinsuffizienz-Behandlung begegnet werden:
Symptomfreie (asymptomatische) Herzinsuffizienz sollte wie folgt behandelt werden:
Obwohl Chemotherapie-bezogene Herzischämie eine ungewöhnliche Erscheinung ist, hat man ein erhöhtes Risiko für akutes Koronarsyndrom assoziiert mit der Anwendung von zellschädigenden (zytotoxischen) und gezielten Krebsmedikamenten.
Tabelle 4: Behandlung von linksventrikulärer Dysfunktion nach einer Krebstherapie mit nicht-reversibler (Typ I) und reversibler (Typ II) Kardiotoxizität
Zeichenerklärung Quelle: Evidence Based Health Care -- Practice guidelines levels of evidence and grades of recommendations used by the National Guideline Clearinghouse (cached)
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Summary The risk of clinical cardiotoxicity increases with a cumulative dose. Studies evaluating cumulative probability of doxorubicin-induced HF have found rates in the range of
The recommended maximum lifetime cumulative dose for doxorubicin is 400-550 mg/m2.
[Explanation of dosage:
For 1.9 m2 body surface area (average for men) these doses are
After treatment with anthracyclines, it is important to reassess cardiac function of all patients to identify asymptomatic patients who are experiencing increased cardiac damage;
and a repeat assessment after 3 weeks confirms the finding; alternative chemotherapeutic options should be discussed, as continuing treatment with an anthracycline carries increased risk for cardiotoxicity. Considerable variation exists in the measurement of LVEF in that factors unrelated to the cancer drug may have a substantial impact on cardiac function. ... the LVEF measurement is a relatively insensitive tool for detecting cardiotoxicity at an early stage. This is largely because no considerable change in LVEF occurs until a critical amount of myocardial damage has taken place, and only comes to the forefront after compensatory mechanisms are exhausted. In addition, the measurement of LVEF presents a number of challenges related to image quality, assumption of LV geometry, load dependency and expertise.
appear to be promising in detecting early subclinical changes in cardiac performance that anticipate a decrease in conventional LVEF. In the last decade, a new approach, based on the use of cardiac biomarkers, in particular troponins, has emerged, and has proven to be a more sensitive and more specific tool for early, real-time identification, assessment and monitoring of anticancer drug-induced cardiac injury [7, 8]. Strong data indicate that troponin detects anticancer drug induced-cardiotoxicity in its earliest phase, long before any reduction in LVEF has occurred Treatment of anthracycline-induced cardiac dysfunction warrants aggressive intervention with standard modalities consistent with treatments for other forms of HF. Treatment of anticancer drug-induced Left Ventricular Dysfunction (LVD) All patients with cancer who are treated with potentially cardiotoxic therapy represent a high-risk group for the development of HF. The use of Angiotensin-Converting Enzyme Inhibitors (ACE-I) and Beta-Blockers (BB) may be highly effective in this setting of patients.
Management of trastuzumab cardiotoxicity Management of trastuzumab-related cardiotoxicity has two distinct aspects:
Symptomatic LVD must be treated with HF treatment:
Asymptomatic LVD should be treated:
Although cardiac ischemia related to chemotherapy administration is an unusual occurrence, an increased risk of acute coronary syndrome has been associated with administration of cytotoxic and targeted agents for cancer treatment
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Frontiers in Pharmacology, March 2013 | Volume 4 | Article 19 | 1
2. Cardiotoxicity of cancer therapeutics: current issues in screening, prevention, and therapy
Richard J. Sheppard 1,2 *, Jenna Berger 2 and Igal A. Sebag 1,2
1: Division of Cardiology, Sir Mortimer B. Davis-Jewish General Hospital and Lady Davis Institute for Medical Research, Montreal, QC, Canada
2: Faculty of Medicine, McGill University, Montreal, QC, Canada
MONOCLONAL ANTIBODY
Trastuzumab (herceptin)
Trastuzumab is a humanized monoclonal antibody aimed at targeting ERB2 (epidermal growth factor receptor 2) on the surface of ERB2 overexpressing tumor cells.
Tyrosine kinase inhibitors
Tyrosine kinase inhibitor's are molecules that were designed to target TKs which are overexpressed in cancer cells. However, they may also inhibit normal aspects of TK functions in non-cancerous cells and may lead to undesirable side effects such as cardiotoxicity and left ventricular failure (Chu et al., 2007)
Imatinib (gleevec)
Imatinib is a TKI, of the ABL kinase, which has been approved and effective for the treatment of malignancies such as chronic myeloid leukemia (CML) and GIST (Garcia-Alvarez et al., 2010). Cardiotoxicity associated with Imatinib has not been well estab- lished. Early clinical trials investigating the utility of Imatinib in GIST treatment had not consistently monitored cardiac function.
Sunitinib (sutent)
Sunitinib is a multi-targeted TKI that prolongs survival in patients with GIST and RCC. It targets vascular endothelial cell growth factor receptors (VEGFR)1-3, platelet derived growth factor receptors (PDGRF) alpha and beta, FMS-like tyrosine kinase-3 (Flt-3), c-kit (stem cell factor receptor), colony stimulating factor 1 receptor (CSF1R), and the ret oncogene product (Chu et al., 2007).
LVEF, left ventricular ejection fraction.
BNP, brain natriuretic peptide.
ESV, end-systolic volume.
LVESD, left ventricular end-systolic diameter.
LVDD, left ventricular end-diastolic diameter.
EDV, end-diastolic volume.
LVEDD, left ventricular end-diastolic diameter.
Trastuzumab associated toxicity usually responds to standard HF treatment or the discontinuation of trastuzumab, although recovery rates may be lower in those who have received prior ACs. The majority of trastuzumab-related cardiac events are asymptomatic declines in LVEF and early detection and management is crucial to recovery.
Echocardiography
As mentioned, patients with cancer are living longer and the acute and late-onset CIC is an ever growing concern. The early detection of systolic or diastolic dysfunction secondary to these agents is an integral part of our management strategies for these patients. Left ventricular ejection fraction
Breast Cancer Res Treat. 2014 February ; 143(3): 531-539. doi:10.1007/s10549-013-2818-1.
Michel G. Khouri, Whitney E. Hornsby, Risum N, Lee W. Jones et al.
Duke Cancer Institute, Duke University Medical Center, Box 3085, Durham, NC 27710, USA
Email: lee.w.jones@dm.duke.edu
Resting 3DE, GLS, and exercise stress 2DE detect subclinical cardiac dysfunction not apparent with resting 2DE in post-DOX breast cancer patients.
Stand: 5. Januar 2016