Kardiotoxische Substanzen in der Onkologie: Was ist zu beachten?

Zusammenfassung

Kardiale Nebenwirkungen von klassischen oder „molecular targeted“-Chemotherapien umfassen myokardiale Dysfunktion oder Kardiomyopathie, Koronartoxizität, Arrhythmien und arterielle Hypertonie. Die Myokardtoxizität als wichtigste Nebenwirkung kann in Typ I (permanent, direkte Myozytennekrosen; klassischer Vertreter Anthrazykline) und Typ II (reversibel, keine Nekrosen; klassischer Vertreter Trastuzumab) unterschieden werden. Eine Früherkennung einer subklinischen Myokardschädigung scheint mittels Speckle-Tracking-Echokardiografie und Troponin-Bestimmungen möglich. Effektive präventive und therapeutische Ansätze zur Minderung der Myokardtoxizität von Anthrazyklinen (verlängerte Infusion, liposomales Doxorubicin, Dexrazoxane, Betablocker, ACE-Hemmer) und von Trastuzumab (Betablocker, ACE-Hemmer) sind verfügbar. Aufgabe des sich entwickelnden Feldes der Kardioonkologie ist die Herstellung einer vernünftigen Balance zwischen onkologischer Effektivität und kardialen Risiken.

Abstract

Cardiac side effects of classical or molecular targeted chemotherapy include myocardial dysfunction or cardiomyopathy, coronary toxicity, arrhythmias and arterial hypertension. Myocardial toxicity can be permanent (type I: myocyte necrosis, typically induced by anthracyclines) or reversible (type II: no myocyte necrosis, typically induced by trastuzumab). Early detection of subclinical myocardial damage may be possible using speckle tracking echocardiography or troponin measurements. Effective preventive and therapeutic strategies to reduce the myocardial toxicity of anthracyclines (prolonged infusion time, liposomal doxorubicin, dexrazoxane, beta-blockers, ACE-inhibitors) and of trastuzumab (beta-blockers, ACE-inhibitors) are available. The evolving field of cardio-oncology has to define the reasonable balance between oncological effectiveness and cardiac risks of modern cancer chemotherapy.

Schlüsselwörter

Chemotherapie - Kardiotoxizität - Anthrazykline - Trastuzumab - Betablocker - ACE-Hemmer

Key words

cancer chemotherapy - cardiotoxicity - anthracyclines - trastuzumab - beta-blockers - ACE-inhibitors

• Literatur

• 1 Eschenhagen T, Force T, Ewer MS et al. Cardiovascular side effects of cancer therapies: a position statement from the Heart Failure Association of the European Society of Cardiology. Eur J Heart Fail 2011; 13: 1-10
• 2 Yancy CW, Jessup M, Bozkurt B et al. 2013 ACCF/AHA guideline for the management of heart failure. Circulation 2013; 128: e240-e327
• 3 Ederhy S, Izzedine H, Massard C et al. Cardiac side effects of molecular targeted therapies: towards a better dialogue between oncologists and cardiologists. Crit Rev Oncol Hematol 2011; 80: 369-379
• 4 Ewer MS, Ewer SM. Cardiotoxicity of anticancer treatments. Nat Rev Cardiol 2015; 12: 547-558
• 5 Hahn VS, Lenihan DJ, Ky B. Cancer therapy-induced cardiotoxicity: basic mechanisms and potential cardioprotective therapies. J Am Heart Assoc 2014; 3: e000665
• 6 Curigliano G, Cardinale D, Suter T et al. Cardiovascular toxicity induced by chemotherapy, targeted agents and radiotherapy: ESMO Clinical Practice Guidelines. Ann Oncol 2012; 23 (Suppl. 07) vii155-vii166
• 7 Yu AF, Steingart RM, Fuster V. Cardiomyopathy associated with cancer therapy. J Cardiac Fail 2014; 20: 841-852
• 8 Negishi K, Negishi T, Haluska BA et al. Use of speckle strain to assess left ventricular responses to cardiotoxic chemotherapy and cardioprotection. Eur Heart J Cardiovasc Imaging 2014; 15: 324-331
• 9 Thavendiranathan P, Poulin F, Lim KD et al. Use of myocardial strain imaging by echocardiography for the early detection of cardiotoxicity in patients during and after cancer chemotherapy. J Am Coll Cardiol 2014; 63: 2751-2768
• 10 Kalam K, Marwick TH. Role of cardioprotective therapy for prevention of cardiotoxicity with chemotherapy: a systematic review and meta-analysis. Eur J Cancer 2013; 49: 2900-2909
• 11 Vejpongsa P, Yeh ET. Prevention of anthracycline-induced cardiotoxicity. J Am Coll Cardiol 2014; 64: 938-945
• 12 Bhave M, Shah AN, Akhter N et al. An update on the risk prediction and prevention of anticancer therapy-induced cardiotoxicity. Curr Opin Oncol 2014; 26: 590-599
• 13 Saif MW, Xyla V, Makrilia N et al. Fluoropyrimidine-associated cardiotoxicity revisited. Expert Opin Drug Saf 2009; 8: 191-202
• 14 Tamargo J, Caballero R, Delpón E. Cancer chemotherapy and cardiac arrhythmias: a review. Drug Saf 2015; 38: 129-152
• 15 Abi Aad S, Pierce M, Barmaimon G et al. Hypertension induced by chemotherapeutic and immunosuppressive agents: a new challenge. Crit Rev Oncol Hematol 2015; 93: 28-35