Cardiac Side-effects of Cancer Chemotherapy

Review Cardiac side-effects of cancer chemotherapy Jean-Jacques Monsuez a, ⁎, Jean-Christophe Charniot b , Noëlle Vignat b , Jean-Yves Artigou b a AP-HP, Hôpital René Muret, Cardiologie, Policlinique médicale, Université Paris-13, Faculté de Médecine de Bobigny, 93270 Sevran, France b AP-HP, Hôpital Avicenne, Service de cardiologie, Université Paris-13, Faculté de Médecine de Bobigny, France a b s t r a c t a r t i c l e i n f o Article history: Received 23 September 2009 Received in revised form 27 February 2010 Accepted 6 March 2010 Available online 18 April 2010 Keywords: Cancer Chemotherapy Cardiotoxicity The spectrum of cardiac side-effect s of cancer chemotherapy has expanded with the development of combination, adjuvan t and target ed chemot herapi es. Their administration in multi ple regimens has increased greatly, including in older patients and in patients with cardiovascular and/or coronary artery disease (CAD). Cardiac toxicity of anthracyclines involves oxidative stress and apoptosis. Early detection combines 2D- echocardiography and/or radionuclide angiography and recent methods such as tissue Doppler imaging, strain rate echocardiography and sampling of serial troponin and/or NT-proBNP levels. Dexraz oxane has proven effecti ve in the prevent ion of dose-r elated toxicit y in children and adults . High doses of the alkylating drugs cyclophosphamide and ifosfamide may result in a reversible heart failure and in life-threatening arrhythmias. Myocardial ischemia induced by the antimetabolites 5-uorouracil and capecitabine impacts prognos is of patients wit h pri or CAD. Severe arrhythmi as may compli cate administration of microtubule inhibitors. Targeted therapies with the antibody-based tyrosine kinases (TK) inhibitors trastuzumab and, to a lesser extent, alemtuzumab induce heart failure or asymptomatic LV dysfunction in 1–4% and 10%, respectively. Cetuximab and rituximab induce hypotension, whereas bevacizumab may promote severe hypertension and venous thromboembolism. Small molecule TK inhibitors may also elicit LV dysfunction, in only few patients treated with imatinib mesylate, but in a substantially higher proportion of those receiving the multitargeted TK inhibitor sunitinib or the recently approved drugs erlotinib, lapatinib and dasatinib. Management of patients at increased cardiovascular risk associated with advancing age, previous CAD or target ed therapies may be optimized by referral to a cardiologis t in a cross- specialty teamwork. © 2010 Elsevier Ireland Ltd. All rights reserved. 1. Introduction Cancer therapy has substantially improved over the past decade with the introduction of combination drug regimens, adjuvant and targeted therapies. As a result, patients in increased numbers and in older age are now treated with successive chemotherapy lines with a signicantl y incr eased survi val. Howev er, the spec trum of cardiac side-eff ects assoc iated with these progres ses has also gradually expanded, including increased recognition of additive cardiac toxicity of anticancer drugs in combination and identication of previously unsuspected concerns associate d with the widespread use of recently introduced targeted therapies. 2. Anthracyclines 2.1. Mechanisms of action Anthracyclines and related compounds are intercalating agents whic h are effective in many malignant disea ses. They compr ise doxorubicin, daunorubicin and its derivative zorubicin, epirubicin, and related drugs including mitoxantrone, bisantrene, aclacinomycin A and ams acr ine , all bei ng ass oci ated wit h a cumulative, dos e- dependent, cardiac toxicity. 2.1.1. Antitumor activity The antitumor activity of anthr acycl ines depends on sever al interconnec ted mechanisms [1,2]: – Cell penetra tion through the multip le drug resist ance (MDR) pore and subsequent proteasome-mediated transport to the nucleus – Intercal ation into nucl ear DNA, whic h is elic ited by the multi planar ring structure of the drug (Fig. 1), impairs transcription and, in turn, protein synthesis International Journal of Cardiology 144 (2010) 3–15 ⁎ Corresponding author. AP-HP, Hôpital René Muret, Policlinique médicale, Avenue du Docteur Schaeffner, F-93270 Sevran, France. Tel.: +33 1 41525884; fax: +33 1 141525863. E-mail address: [email protected] (J.-J. Monsuez). 0167-5273/$ – see front matter © 2010 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijcard.2010.03.003 Contents lists available at ScienceDirect International Journal of Cardiology j o ur n a l h omepag e: www. el s ev i e r. c o m/ l o ca t e / i j ca r d

Cardiac Side-effects of Cancer Chemotherapy

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