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Targeted Cancer Therapies and QT Interval Prolongation: Unveiling the Mechanisms Underlying Arrhythmic Complications and the Need for Risk Stratification Strategies

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Abstract

The care and treatment of cancer patients has significantly changed in the last decade with a remarkable shift towards novel targeted therapies. These promising new drugs may represent effective and potentially life-saving therapeutic options in cancer patients, but are also emerging in the cardiotoxicity scenario for their arrhythmogenic potential due to their QT-prolonging activity. In this article we review the mechanisms underlying drug-induced QT interval prolongation and the classes of anticancer-targeted therapies most frequently responsible for this adverse event, with a particular focus on tyrosine kinase-targeting molecules. Since up to 49 % of serious adverse drug reactions (ADRs) and 58 % of potentially fatal ADRs may not appear on initial drug safety labels, we also review and discuss data from the post-marketing VigiBase® safety reporting system, the World Health Organization’s global database of ADRs. Finally, we discuss arrhythmic risk stratification and prevention strategies in the complex multiple-risk setting of cancer patients, paying particular attention to drug–drug interactions with common antimicrobial, psychotropic and antiemetic supportive care, and we also provide an electrocardiographic QT monitoring algorithm for patients who are candidates for targeted cancer therapies.

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References

  1. Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2014;136(5):E359–86. doi:10.1002/ijc.29210.

    Article  PubMed  Google Scholar 

  2. Suter TM, Ewer MS. Cancer drugs and the heart: importance and management. Eur Heart J. 2013;34(15):1102–11. doi:10.1093/eurheartj/ehs181.

    Article  CAS  PubMed  Google Scholar 

  3. Curigliano G, Cardinale D, Suter T, Plataniotis G, de Azambuja E, Sandri MT, ESMO Guidelines Working Group, et al. Cardiovascular toxicity induced by chemotherapy, targeted agents and radiotherapy: ESMO Clinical Practice Guidelines. Ann Oncol. 2012;23(Suppl 7):vii155–66. doi:10.1093/annonc/mds293.

  4. Raschi E, de Ponti F. Cardiovascular toxicity of anticancer-targeted therapy: emerging issues in the era of cardio-oncology. Intern Emerg Med. 2012;7(2):113–31. doi:10.1007/s11739-011-0744-y.

    Article  PubMed  Google Scholar 

  5. Raschi E, Vasina V, Ursino MG, Boriani G, Martoni A, de Ponti F. Anticancer drugs and cardiotoxicity: insights and perspectives in the era of targeted therapy. Pharmacol Ther. 2010;125(2):196–218. doi:10.1016/j.pharmthera.2009.10.002.

    Article  CAS  PubMed  Google Scholar 

  6. Force T, Kerkelä R. Cardiotoxicity of the new cancer therapeutics–mechanisms of, and approaches to, the problem. Drug Discov Today. 2008;13(17–18):778–84. doi:10.1016/j.drudis.2008.05.011.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Albini A, Pennesi G, Donatelli F, Cammarota R, De Flora S, Noonan DM. Cardiotoxicity of anticancer drugs: the need for cardio-oncology and cardio-oncological prevention. J Natl Cancer Inst. 2010;102(1):14–25. doi:10.1093/jnci/djp440.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Eschenhagen T, Force T, Ewer MS, de Keulenaer GW, Suter TM, Anker SD, 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):1–10. doi:10.1093/eurjhf/hfq213.

    Article  PubMed  Google Scholar 

  9. Lal H, Kolaja KL, Force T. Cancer genetics and the cardiotoxicity of the therapeutics. J Am Coll Cardiol. 2013;61(3):267–74. doi:10.1016/j.jacc.2012.05.066.

    Article  CAS  PubMed  Google Scholar 

  10. Hahn VS, Lenihan DJ, Ky B. Cancer therapy-induced cardiotoxicity: basic mechanisms and potential cardioprotective therapies. J Am Heart Assoc. 2014;3(2):e000665. doi:10.1161/JAHA.113.000665.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Ewer MS, Von Hoff DD, Benjamin RS. A historical perspective of anthracycline cardiotoxicity. Heart Fail Clin. 2011;7(3):363–72. doi:10.1016/j.hfc.2011.03.001.

    Article  PubMed  Google Scholar 

  12. Schwartz PJ, Crotti L, Insolia R. Long-QT syndrome: from genetics to management. Circ Arrhythm Electrophysiol. 2012;5(4):868–77. doi:10.1161/CIRCEP.111.962019.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Kapplinger JD, Tester DJ, Salisbury BA, et al. Spectrum and prevalence of mutations from the first 2,500 consecutive unrelated patients referred for the FAMILION long QT syndrome genetic test. Heart Rhythm. 2009;6(9):1297–303. doi:10.1016/j.hrthm.2009.05.021.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Roden DM, Viswanathan PC. Genetics of acquired long QT syndrome. J Clin Invest. 2005;115(8):2025–32. doi:10.1172/JCI25539.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Kannankeril P, Roden DM, Darbar D. Drug-induced long QT syndrome. Pharmacol Rev. 2010;62(4):760–81. doi:10.1124/pr.110.003723.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Mitcheson JS, Chen J, Lin M, Culberson C, Sanguinetti MC. A structural basis for drug-induced long QT syndrome. Proc Natl Acad Sci USA. 2000;97(22):12329–33. doi:10.1073/pnas.210244497.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Fernandez D, Ghanta A, Kauffman GW, Sanguinetti MC. Physicochemical features of the HERG channel drug binding site. J Biol Chem. 2004;279(11):10120–7. doi:10.1074/jbc.M310683200.

    Article  CAS  PubMed  Google Scholar 

  18. Yeung K-S, Meanwell NA. Inhibition of hERG channel trafficking: an under-explored mechanism for drug-induced QT prolongation. ChemMedChem. 2008;3(10):1501–2. doi:10.1002/cmdc.200800170.

    Article  CAS  PubMed  Google Scholar 

  19. Kolecki PF, Curry SC. Poisoning by sodium channel blocking agents. Crit Care Clin. 1997;13(4):829–48.

    Article  CAS  PubMed  Google Scholar 

  20. Niemeijer MN, Van Den Berg ME, Eijgelsheim M. Pharmacogenetics of drug-induced QT interval prolongation: an update. Drug Saf. 2015;38(10):855–67. doi:10.1007/s40264-015-0316-6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Antzelevitch C. Cellular basis for the repolarization waves of the ECG. Ann N Y Acad Sci. 2006;1080:268–81. doi:10.1196/annals.1380.021.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Antzelevitch C. Role of spatial dispersion of repolarization in inherited and acquired sudden cardiac death syndromes. Am J Physiol Heart Circ Physiol. 2007;293(4):H2024–38. doi:10.1152/ajpheart.00355.2007.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Frommeyer G, Eckardt L. Drug-induced proarrhythmia: risk factors and electrophysiological mechanisms. Nat Rev Cardiol. 2016;13(1):36–47. doi:10.1038/nrcardio.2015.110.

    Article  CAS  PubMed  Google Scholar 

  24. de Bruyne MC, Hoes AW, Kors JA, Hofman A, van Bemmel JH, Grobbee DE. QTc dispersion predicts cardiac mortality in the elderly: the Rotterdam Study. Circulation. 1998;97(5):467–72.

    Article  PubMed  Google Scholar 

  25. Molokhia M, Pathak A, Lapeyre-Mestre M, Caturla L, Montastruc JL, McKeigue P. Case ascertainment and estimated incidence of drug-induced long-QT syndrome: study in Southwest France. Br J Clin Pharmacol. 2008;66(3):386–95. doi:10.1111/j.1365-2125.2008.03229.x.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Sarganas G, Garbe E, Klimpel A, Hering RC, Bronder E, Haverkamp W. Epidemiology of symptomatic drug-induced long QT syndrome and Torsade de Pointes in Germany. Europace. 2014;16(1):101–8. doi:10.1093/europace/eut214.

    Article  PubMed  Google Scholar 

  27. Brell JM. Prolonged QTc interval in cancer therapeutic drug development: defining arrhythmic risk in malignancy. Prog Cardiovasc Dis. 2010;53(2):164–72. doi:10.1016/j.pcad.2010.05.005.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. E14 Implementation Working Group. ICH E14 Guideline: The clinical evaluation of QT/QTc interval prolongation and proarrhythmic potential for non-antiarrhythmic drugs. Questions & Answers (R2). Geneva: International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use; 2014.

  29. Drew BJ, Ackerman MJ, Funk M, Gibler WB, Kligfield P, Menon V, American Heart Association Acute Cardiac Care Committee of the Council on Clinical Cardiology, the Council on Cardiovascular Nursing, and the American College of Cardiology Foundation, et al. Prevention of torsade de pointes in hospital settings: a scientific statement from the American Heart Association and the American College of Cardiology Foundation. Circulation. 2010;121(8):1047–60. doi:10.1161/CIRCULATIONAHA.109.192704.

    Article  PubMed  PubMed Central  Google Scholar 

  30. 4.0 C version. Common Terminology Criteria for adverse events (CTCAE). http://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03_2010-06-14_QuickReference_5x7.pdf. Accessed 22 May 2016.

  31. Naing A, Veasey-Rodrigues H, Hong DS, Fu S, Falchook GS, Wheler JJ, et al. Electrocardiograms (ECGs) in phase I anticancer drug development: the MD Anderson Cancer Center experience with 8518 ECGs. Ann Oncol. 2012;23(11):2960–3. doi:10.1093/annonc/mds130.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Varterasian M, Meyer M, Fingert H, Radlowski D, Asbury P, Zhou X, et al. Baseline heart rate-corrected QT and eligibility for clinical trials in oncology. J Clin Oncol. 2003;21(17):3378–9. doi:10.1200/JCO.2003.99.104.

    Article  PubMed  Google Scholar 

  33. Varterasian M, Fingert H, Agin M, Meyer M. Consideration of QT/QTc interval data in a phase I study in patients with advanced cancer [letter]. Clin Cancer Res. 2004;10(17):5967–5968; author reply 5968–5969. doi:10.1158/1078-0432.CCR-04-0534.

  34. Zeltser D, Justo D, Halkin A, Prokhorov V, Heller K, Viskin S. Torsade de pointes due to noncardiac drugs: most patients have easily identifiable risk factors. Medicine (Baltimore). 2003;82(4):282–90. doi:10.1097/01.md.0000085057.63483.9b.

    PubMed  Google Scholar 

  35. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144(5):646–74. doi:10.1016/j.cell.2011.02.013.

    Article  CAS  PubMed  Google Scholar 

  36. Locatelli M, Criscitiello C, Esposito A, Minchella I, Goldhirsch A, Cipolla C, et al. QTc prolongation induced by targeted biotherapies used in clinical practice and under investigation: a comprehensive review. Target Oncol. 2015;10(1):27–43. doi:10.1007/s11523-014-0325-x.

    Article  PubMed  Google Scholar 

  37. Manning G, Whyte DB, Martinez R, Hunter T, Sudarsanam S. The protein kinase complement of the human genome. Science. 2002;298(5600):1912–34. doi:10.1126/science.1075762.

    Article  CAS  PubMed  Google Scholar 

  38. Druker BJ, Talpaz M, Resta DJ, Peng B, Buchdunger E, Ford JM, et al. Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia. N Engl J Med. 2001;344(14):1031–7. doi:10.1056/NEJM200104053441401.

    Article  CAS  PubMed  Google Scholar 

  39. Bosutinib, BOSULIF [prescribing information]. http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/203341lbl.pdf. Accessed 29 May 2016.

  40. Ceritinib, ZYCADIA. Supplemental approval. http://www.accessdata.fda.gov/drugsatfda_docs/appletter/2015/205755Orig1s003,s004ltr.pdf. Accessed 29 May 2016.

  41. Crizotinib, XALKORI [prescribing information]. http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/202570s002lbl.pdf. Accessed 29 May 2016.

  42. Dasatinib, SRPYCEL [prescribing information]. http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/021986s7s8lbl.pdf. Accessed 29 May 2016.

  43. Lenvatanib, LENVIMA [prescribing information]. http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/206947s000lbl.pdf. Accessed 29 May 2016.

  44. Nilotinib, TASIGNA [prescribing information]. http://www.accessdata.fda.gov/drugsatfda_docs/label/2007/022068lbl.pdf. Accessed 29 May 2016.

  45. Osimertinib, TAGRISSO [prescribing information]. http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/208065s000lbl.pdf. Accessed 29 May 2016.

  46. Pazopanib, VOTRIENT [prescribing information]. https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/022465lbl.pdf. Accessed 29 May 2016.

  47. Ponatinib, ICLUSIG [prescribing information]. http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/203469lbl.pdf. Accessed 29 May 2016.

  48. Sorafenib, NEXAVAR [prescribing information]. http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/021923s008s009lbl.pdf. Accessed 29 May 2016.

  49. Sunitinib malate, SUTENT [prescribing information]. http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/021938s13s17s18lbl.pdf. Accessed 29 May 2016.

  50. US FDA. Vandetanib, CAPRELSA. Risk evaluation and mitigation strategy. http://www.fda.gov/downloads/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/UCM253441.pdf. Accessed 29 May 2016.

  51. Woosley R, Romero K. QT drugs list. https://crediblemeds.org/. Accessed 22 May 2016.

  52. Ghatalia P, Je Y, Kaymakcalan MD, Sonpavde G, Choueiri TK. QTc interval prolongation with vascular endothelial growth factor receptor tyrosine kinase inhibitors. Br J Cancer. 2015;112(2):296–305. doi:10.1038/bjc.2014.564.

    Article  CAS  PubMed  Google Scholar 

  53. Lu Z, Wu C-YC, Jiang Y-P, Ballou LM, Clausen C, Cohen IS, et al. Suppression of phosphoinositide 3-kinase signaling and alteration of multiple ion currents in drug-induced long QT syndrome. Sci Transl Med. 2012;4(131):131ra50. doi:10.1126/scitranslmed.3003623.

  54. Shah RR, Morganroth J, Shah DR. Cardiovascular safety of tyrosine kinase inhibitors: with a special focus on cardiac repolarisation (QT Interval). Drug Saf. 2013;36(5):295–316. doi:10.1007/s40264-013-0047-5.

    Article  CAS  PubMed  Google Scholar 

  55. Jeong W, Doroshow JH, Kummar S. United States Food and Drug Administration approved oral kinase inhibitors for the treatment of malignancies. Curr Probl Cancer. 2013;37(3):110–44. doi:10.1016/j.currproblcancer.2013.06.001.

    Article  PubMed  PubMed Central  Google Scholar 

  56. Fraczek J, Vanhaecke T, Rogiers V. Toxicological and metabolic considerations for histone deacetylase inhibitors. Expert Opin Drug Metab Toxicol. 2013;9(4):441–57. doi:10.1517/17425255.2013.754011.

    Article  CAS  PubMed  Google Scholar 

  57. Noonan AM, Eisch RA, Liewehr DJ, Sissung TM, Venzon DJ, Flagg TP, et al. Electrocardiographic studies of romidepsin demonstrate its safety and identify a potential role for KATP channel. Clin Cancer Res. 2013;19(11):3095–104. doi:10.1158/1078-0432.CCR-13-0109.

    Article  CAS  PubMed  Google Scholar 

  58. Munster PN, Rubin EH, Van Belle S, Friedman E, Patterson JK, Van Dyck K, et al. A single supratherapeutic dose of vorinostat does not prolong the QTc interval in patients with advanced cancer. Clin Cancer Res. 2009;15(22):7077–84. doi:10.1158/1078-0432.CCR-09-1214.

    Article  CAS  PubMed  Google Scholar 

  59. Siemann DW, Chaplin DJ. An update on the clinical development of drugs to disable tumor vasculature. Expert Opin Drug Discov. 2007;2(10):1357–67. doi:10.1517/17460441.2.10.1357.

    Article  CAS  PubMed  Google Scholar 

  60. McKeage MJ, Baguley BC. Disrupting established tumor blood vessels: an emerging therapeutic strategy for cancer. Cancer. 2010;116(8):1859–71. doi:10.1002/cncr.24975.

    Article  CAS  PubMed  Google Scholar 

  61. Milan A, Puglisi E, Ferrari L, Bruno G, Losano I, Veglio F. Arterial hypertension and cancer. Int J Cancer. 2014;134(10):2269–77. doi:10.1002/ijc.28334.

    Article  CAS  PubMed  Google Scholar 

  62. Dowlati A, Robertson K, Cooney M, Petros WP, Stratford M, Jesberger J, et al. A phase I pharmacokinetic and translational study of the novel vascular targeting agent combretastatin A-4 phosphate on a single-dose intravenous schedule in patients with advanced cancer. Cancer Res. 2002;62(12):3408–16.

    CAS  PubMed  Google Scholar 

  63. Ibrahim MA, Do DV, Sepah YJ, Shah SM, Van Anden E, Hafiz G, et al. Vascular disrupting agent for neovascular age related macular degeneration: a pilot study of the safety and efficacy of intravenous combretastatin A-4 phosphate. BMC Pharmacol Toxicol. 2013;14(1):7. doi:10.1186/2050-6511-14-7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Bos JL. Ras oncogenes in human cancer: a review. Cancer Res. 1989;49(17):4682–9.

    CAS  PubMed  Google Scholar 

  65. Mazieres J, Pradines A, Favre G. Perspectives on farnesyl transferase inhibitors in cancer therapy. Cancer Lett. 2004;206(2):159–67. doi:10.1016/j.canlet.2003.08.033.

    Article  CAS  PubMed  Google Scholar 

  66. Roffey J, Rosse C, Linch M, Hibbert A, McDonald NQ, Parker PJ. Protein kinase C intervention-the state of play. Curr Opin Cell Biol. 2009;21(2):268–79. doi:10.1016/j.ceb.2009.01.019.

    Article  CAS  PubMed  Google Scholar 

  67. Murray NR, Kalari KR, Fields AP. Protein kinase C?? expression and oncogenic signaling mechanisms in cancer. J Cell Physiol. 2011;226(4):879–87. doi:10.1002/jcp.22463.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Kreisl TN, Kim L, Moore K, Duic P, Kotliarova S, Walling J, et al. A phase I trial of enzastaurin in patients with recurrent gliomas. Clin Cancer Res. 2009;15(10):3617–23. doi:10.1158/1078-0432.CCR-08-3071.

    Article  CAS  PubMed  Google Scholar 

  69. Seruga B, Sterling L, Wang L, Tannock IF. Reporting of serious adverse drug reactions of targeted anticancer agents in pivotal phase III clinical trials. J Clin Oncol. 2011;29(2):174–85. doi:10.1200/JCO.2010.31.9624.

    Article  CAS  PubMed  Google Scholar 

  70. World Health Organization Collaborating Centre for International Drug Monitoring. VigiAccess™. http://www.vigiaccess.org. Accessed 2 Jun 2016.

  71. Schwartz PJ, Woosley RL. Predicting the unpredictable: drug-induced QT prolongation and Torsades de Pointes. J Am Coll Cardiol. 2016;67(13):1639–50. doi:10.1016/j.jacc.2015.12.063.

    Article  PubMed  Google Scholar 

  72. Shah RR, Morganroth J. Update on cardiovascular safety of tyrosine kinase inhibitors: with a special focus on QT interval, left ventricular dysfunction and overall risk/benefit. Drug Saf. 2015;38(8):693–710. doi:10.1007/s40264-015-0300-1.

    Article  CAS  PubMed  Google Scholar 

  73. Tuccori M, Montagnani S, Capogrosso-Sansone A, Mantarro S, Antonioli L, Fornai M, et al. Adverse reactions to oncologic drugs: spontaneous reporting and signal detection. Expert Rev Clin Pharmacol. 2015;8(1):61–75.

    Article  PubMed  Google Scholar 

  74. Antman KH. Introduction: the history of arsenic trioxide in cancer therapy. Oncologist. 2001;6(Suppl 2):1–2.

    Article  CAS  PubMed  Google Scholar 

  75. Barbey JT, Pezzullo JC, Soignet SL. Effect of arsenic trioxide on QT interval in patients with advanced malignancies. J Clin Oncol. 2003;21(19):3609–15. doi:10.1200/JCO.2003.10.009.

    Article  CAS  PubMed  Google Scholar 

  76. Abo-Salem E, Fowler JC, Attari M, Cox CD, Perez-Verdia A. Antibiotic-induced cardiac arrhythmias. Cardiovasc Ther. 2014;32(1):19–25. doi:10.1111/1755-5922.12054.

    Article  CAS  PubMed  Google Scholar 

  77. Shaffer D, Singer S, Korvick J, Honig P. Concomitant risk factors in reports of Torsades de Pointes associated with macrolide use: review of the United States Food and Drug Administration Adverse Event Reporting System. Clin Infect Dis. 2002;35(2):197–200.

    Article  PubMed  Google Scholar 

  78. Frothingham R. Rates of Torsades de Pointes associated with ciprofloxacin, ofloxacin, levofloxacin, gatifloxacin, and moxifloxacin. Pharmacotherapy. 2001;21(12):1468–72.

    Article  CAS  PubMed  Google Scholar 

  79. Niedrig D, Maechler S, Hoppe L, Corti N, Kovari H. Drug safety of macrolide and quinolone antibiotics in a tertiary care hospital: administration of interacting co-medication and QT prolongation. Eur J Clin Pharmacol. 2016;72(7):859–67. doi:10.1007/s00228-016-2043-z.

    Article  CAS  PubMed  Google Scholar 

  80. FDA. FDA drug safety communication: revised recommentations for Celexa (citalopram hydrobromide) related to a potential risk of abnormal heart rhythms with high doses. http://www.fda.gov/Drugs/DrugSafety/ucm297391.htm. Accessed 22 May 2016.

  81. Barni S, Petrelli F, Cabiddu M. Cardiotoxicity of antiemetic drugs in oncology: an overview of the current state of the art. Crit Rev Oncol Hematol. 2016;102:125–34. doi:10.1016/j.critrevonc.2016.04.012.

    Article  PubMed  Google Scholar 

  82. Maurea N, Spallarossa P, Cadeddu C, Madonna R, Mele D, Monte I, et al. A recommended practical approach to the management of target therapy and angiogenesis inhibitors cardiotoxicity: an opinion paper of the working group on drug cardiotoxicity and cardioprotection, Italian Society of Cardiology. J Cardiovasc Med (Hagerstown). 2016;17(Suppl 1):S93–104. doi:10.2459/JCM.0000000000000383.

    Article  CAS  PubMed Central  Google Scholar 

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  1. Department of Cardiology, Azienda Ospedaliera Ordine Mauriziano, Largo Filippo Turati nr. 62, 10128, Turin, Italy

    Rezarta Cuni, Iris Parrini & Maria Rosa Conte

  2. Azienda Sanitaria Locale Torino 2 and Torino 3, Out of Hospital Cardiology Service, Turin, Italy

    Riccardo Asteggiano

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Rezarta Cuni, Iris Parrini, Riccardo Asteggiano and Maria Rosa Conte have no conflicts of interest to declare regarding the presented work.

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Cuni, R., Parrini, I., Asteggiano, R. et al. Targeted Cancer Therapies and QT Interval Prolongation: Unveiling the Mechanisms Underlying Arrhythmic Complications and the Need for Risk Stratification Strategies. Clin Drug Investig 37, 121–134 (2017). https://doi.org/10.1007/s40261-016-0460-5

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