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Current Drug Therapy

Editor-in-Chief

ISSN (Print): 1574-8855
ISSN (Online): 2212-3903

Research Article

Prevalence of Major Cardiac Events of Anthracycline-Induced Cardiotoxicity in Southwestern Iran: Different Response Patterns to Cumulative Dose

Author(s): Mahsa Behrouzian, Babak Najibi, Sabahat Haghi, Chehreh Mahdavi, Kaveh Jaseb* and Ehsan Ghaedi*

Volume 15, Issue 1, 2020

Page: [78 - 84] Pages: 7

DOI: 10.2174/1574885514666190311145607

Price: $65

Abstract

Background: Anthracyclines are widely used chemotherapeutic agents in several cancers. Since its use, survival improved significantly among cancer patients and has been reported to be up to 80%. However, anthracyclines possess several cardiac, renal and hematological toxicities which limit their use in practice. Cardiotoxicity is still the most important and dose-limiting side effect of anthracycline treatment. Here we aimed to investigate the frequency of anthracyclineinduced cardiomyopathy in pediatric malignancies in Khuzestan Province, Iran.

Methods: A total of 112 patients were enrolled in the present study. Patients were allocated to the case or control group based on receiving anthracycline. Echocardiographic examinations were performed by a cardiologist. Electrocardiograms were also recorded.

Results: We showed that cancer patients who underwent anthracycline treatment showed cardiomyopathy as defined by lower LVEF (Left Ventricular Ejection Fraction) among patients (p = 0.041). Abnormal LVEF was reported with a frequency of about 9.5% in patients (p = 0.026). However, LVFS (Left Ventricular Fraction Shortening), QRS voltage and QT interval did not differ significantly between treatment and control groups. Our data analysis revealed that this difference is mainly related to high cumulative dose since high cumulative dose of anthracycline (>300 mg/m2) leads to lower LVEF and LVFS and higher QRS voltage in comparison with lower cumulative dose (<300 mg/m2) and control group; but there was no significant difference between low dose and control group. Different age groups and type of malignancy including hematological and solid tumors did not show any significant differences for echocardiographic and electrocardiograms parameters.

Conclusion: In our study, lower LVEF among patients who received anthracyclines were mainly related to a high cumulative dose of anthracyclines, which emphasizes the effect of cumulative dose for cardiotoxic effects. Larger studies are needed to investigate possible other risk factors for cardiotoxicity.

Keywords: Anthracyclines, cardiotoxicity, prevalence, cancer, cumulative dose, chemotherapeutic.

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[1]
Gregory SA, Trümper L. Chemotherapy dose intensity in non-Hodgkin’s lymphoma: Is dose intensity an emerging paradigm for better outcomes? Ann Oncol 2005; 16(9): 1413-24.
[http://dx.doi.org/10.1093/annonc/mdi264] [PMID: 15932900]
[2]
Christiansen S, Autschbach R. Doxorubicin in experimental and clinical heart failure. Eur J Cardiothorac Surg 2006; 30(4): 611-6.
[http://dx.doi.org/10.1016/j.ejcts.2006.06.024] [PMID: 16901709]
[3]
Withrow SJ, Page R, Vail DM. Withrow and MacEwen's Small Animal Clinical Oncology-E-Book: Elsevier Health Sciences. 2013.
[4]
Gatta G, Capocaccia R, Coleman MP, Ries LAG, Berrino F. Childhood cancer survival in Europe and the United States. Cancer 2002; 95(8): 1767-72.
[http://dx.doi.org/10.1002/cncr.10833] [PMID: 12365026]
[5]
Ayla S, Seckin I, Tanriverdi G, et al. Doxorubicin induced nephrotoxicity: protective effect of nicotinamide. Int J Cell Biol 2011; 2011: Article ID 390238.
[http://dx.doi.org/10.1155/2011/390238]
[6]
Trachtenberg BH, Landy DC, Franco VI, et al. Anthracycline-associated cardiotoxicity in survivors of childhood cancer. Pediatr Cardiol 2011; 32(3): 342-53.
[http://dx.doi.org/10.1007/s00246-010-9878-3] [PMID: 21221562]
[7]
Lipshultz SE, Alvarez JA, Scully RE. Anthracycline associated cardiotoxicity in survivors of childhood cancer. Heart 2008; 94(4): 525-33.
[http://dx.doi.org/10.1136/hrt.2007.136093] [PMID: 18347383]
[8]
van Dalen EC, van den Brug M, Caron HN, Kremer LC. Anthracycline-induced cardiotoxicity: comparison of recommendations for monitoring cardiac function during therapy in paediatric oncology trials. Eur J Cancer 2006; 42(18): 3199-205.
[http://dx.doi.org/10.1016/j.ejca.2006.08.002] [PMID: 17011186]
[9]
Lipshultz SE, Colan SD, Gelber RD, Perez-Atayde AR, Sallan SE, Sanders SP. Late cardiac effects of doxorubicin therapy for acute lymphoblastic leukemia in childhood. N Engl J Med 1991; 324(12): 808-15.
[http://dx.doi.org/10.1056/NEJM199103213241205] [PMID: 1997853]
[10]
Broeyer FJ, Osanto S, Suzuki J, et al. Evaluation of lecithinized human recombinant super oxide dismutase as cardioprotectant in anthracycline-treated breast cancer patients. Br J Clin Pharmacol 2014; 78(5): 950-60.
[http://dx.doi.org/10.1111/bcp.12429] [PMID: 24844787]
[11]
Kharin SN, Krandycheva VV, Strelkova MV, Tsvetkova AS, Shmakov DN. Doxorubicin-induced changes of ventricular repolarization heterogeneity: Results of a chronic rat study. Cardiovasc Toxicol 2012; 12(4): 312-7.
[http://dx.doi.org/10.1007/s12012-012-9172-0] [PMID: 22618330]
[12]
Pongprot Y, Sittiwangkul R, Charoenkwan P, Silvilairat S. Use of cardiac markers for monitoring of doxorubixin-induced cardiotoxicity in children with cancer. J Pediatr Hematol Oncol 2012; 34(8): 589-95.
[http://dx.doi.org/10.1097/MPH.0b013e31826faf44] [PMID: 23018571]
[13]
Di Marco A, Cassinelli G, Arcamone F. The discovery of daunorubicin. Cancer Treat Rep 1981; 65(Suppl. 4): 3-8.
[PMID: 7049379]
[14]
Von Hoff DD, Layard MW, Basa P, et al. Risk factors for doxorubicin-induced congestive heart failure. Ann Intern Med 1979; 91(5): 710-7.
[http://dx.doi.org/10.7326/0003-4819-91-5-710] [PMID: 496103]
[15]
Temming P, Qureshi A, Hardt J, et al. Prevalence and predictors of anthracycline cardiotoxicity in children treated for acute myeloid leukaemia: retrospective cohort study in a single centre in the United Kingdom. Pediatr Blood Cancer 2011; 56(4): 625-30.
[http://dx.doi.org/10.1002/pbc.22908] [PMID: 21298750]
[16]
Buzdar AU, Marcus C, Smith TL, Blumenschein GR. Early and delayed clinical cardiotoxicity of doxorubicin. Cancer 1985; 55(12): 2761-5.
[http://dx.doi.org/10.1002/1097-0142(19850615)55:12<2761:AID-CNCR2820551206>3.0.CO;2-P] [PMID: 3922612]
[17]
Swain SM, Whaley FS, Ewer MS. Congestive heart failure in patients treated with doxorubicin: a retrospective analysis of three trials. Cancer 2003; 97(11): 2869-79.
[http://dx.doi.org/10.1002/cncr.11407] [PMID: 12767102]
[18]
Kremer LC, van Dalen EC, Offringa M, Ottenkamp J, Voûte PA. Anthracycline-induced clinical heart failure in a cohort of 607 children: long-term follow-up study. J Clin Oncol 2001; 19(1): 191-6.
[http://dx.doi.org/10.1200/JCO.2001.19.1.191] [PMID: 11134212]
[19]
Mulrooney DA, Yeazel MW, Kawashima T, et al. Cardiac outcomes in a cohort of adult survivors of childhood and adolescent cancer: retrospective analysis of the childhood cancer survivor study cohort. BMJ 2009; 339: b4606.
[http://dx.doi.org/10.1136/bmj.b4606] [PMID: 19996459]
[20]
Grenier MA, Lipshultz SE, Eds. Epidemiology of anthracycline cardiotoxicity in children and adultsSeminars in oncology. 1998.
[21]
Kremer LC, van Dalen EC, Offringa M, Voûte PA. Frequency and risk factors of anthracycline-induced clinical heart failure in children: a systematic review. Ann Oncol 2002; 13(4): 503-12.
[http://dx.doi.org/10.1093/annonc/mdf118] [PMID: 12056699]
[22]
Lipshultz SE, Lipsitz SR, Sallan SE, et al. Chronic progressive cardiac dysfunction years after doxorubicin therapy for childhood acute lymphoblastic leukemia. J Clin Oncol 2005; 23(12): 2629-36.
[http://dx.doi.org/10.1200/JCO.2005.12.121] [PMID: 15837978]
[23]
Wojnowski L, Kulle B, Schirmer M, et al. NAD(P)H oxidase and multidrug resistance protein genetic polymorphisms are associated with doxorubicin-induced cardiotoxicity. Circulation 2005; 112(24): 3754-62.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.105.576850] [PMID: 16330681]
[24]
Monsuez JJ, Charniot JC, Vignat N, Artigou JY. Cardiac side-effects of cancer chemotherapy. Int J Cardiol 2010; 144(1): 3-15.
[http://dx.doi.org/10.1016/j.ijcard.2010.03.003] [PMID: 20399520]
[25]
Godoy L, Fukushige J, Igarashi H, Matsuzaki A, Ueda K. Anthracycline‐induced cardiotoxicity in children with malignancies. Pediatr Int 1997; 39: 188-93.
[http://dx.doi.org/10.1111/j.1442-200X.1997.tb03579.x]
[26]
Steinberg JS, Cohen AJ, Wasserman AG, Cohen P, Ross AM. Acute arrhythmogenicity of doxorubicin administration. Cancer 1987; 60(6): 1213-8.
[http://dx.doi.org/10.1002/1097-0142(19870915)60:6<1213:AID-CNCR2820600609>3.0.CO;2-V] [PMID: 3621107]
[27]
Davies KJ, Doroshow JH. Redox cycling of anthracyclines by cardiac mitochondria. I. Anthracycline radical formation by NADH dehydrogenase. J Biol Chem 1986; 261(7): 3060-7.
[PMID: 3456345]
[28]
Minotti G, Recalcati S, Menna P, Salvatorelli E, Corna G, Cairo G. Doxorubicin cardiotoxicity and the control of iron metabolism: quinone-dependent and independent mechanisms Methods in enzymology 378. Elsevier 2004; pp. 340-61.
[29]
Minotti G, Menna P, Salvatorelli E, Cairo G, Gianni L. Anthracyclines: molecular advances and pharmacologic developments in antitumor activity and cardiotoxicity. Pharmacol Rev 2004; 56(2): 185-229.
[http://dx.doi.org/10.1124/pr.56.2.6] [PMID: 15169927]
[30]
Volkova M, Palmeri M, Russell KS, Russell RR. Activation of the aryl hydrocarbon receptor by doxorubicin mediates cytoprotective effects in the heart. Cardiovasc Res 2011; 90(2): 305-14.
[http://dx.doi.org/10.1093/cvr/cvr007] [PMID: 21233252]
[31]
Grethe S, Coltella N, Di Renzo MF, Pörn-Ares MI. p38 MAPK downregulates phosphorylation of Bad in doxorubicin-induced endothelial apoptosis. Biochem Biophys Res Commun 2006; 347(3): 781-90.
[http://dx.doi.org/10.1016/j.bbrc.2006.06.159] [PMID: 16843435]
[32]
Finck BN, Kelly DP. Peroxisome proliferator-activated receptor γ coactivator-1 (PGC-1) regulatory cascade in cardiac physiology and disease. Circulation 2007; 115(19): 2540-8.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.107.670588] [PMID: 17502589]
[33]
Ma J, Wang Y, Zheng D, Wei M, Xu H, Peng T. Rac1 signalling mediates doxorubicin-induced cardiotoxicity through both reactive oxygen species-dependent and -independent pathways. Cardiovasc Res 2013; 97(1): 77-87.
[http://dx.doi.org/10.1093/cvr/cvs309] [PMID: 23027656]
[34]
McGowan JV, Chung R, Maulik A, Piotrowska I, Walker JM, Yellon DM. Anthracycline chemotherapy and cardiotoxicity. Cardiovasc Drugs Ther 2017; 31(1): 63-75.
[http://dx.doi.org/10.1007/s10557-016-6711-0] [PMID: 28185035]
[35]
Geisberg CA, Sawyer DB. Mechanisms of anthracycline cardiotoxicity and strategies to decrease cardiac damage. Curr Hypertens Rep 2010; 12(6): 404-10.
[http://dx.doi.org/10.1007/s11906-010-0146-y] [PMID: 20842465]

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