Pharmacological interventions for preventing anthracycline-induced clinical and subclinical cardiotoxicity: A network meta-analysis of metastatic breast cancer
Restricted accessReview articleFirst published online March, 2021
Pharmacological interventions for preventing anthracycline-induced clinical and subclinical cardiotoxicity: A network meta-analysis of metastatic breast cancer
Doxorubicin- and epirubicin-induced cardiotoxicities are life threatening for those suffering from breast cancer. Comparing the effects of different strategies on the prevention of these agent-induced cardiotoxicities remains unexplored.
Data sources: A comprehensive review of clinical trials was performed on the prevention of epirubicin- and/or doxorubicin-induced cardiotoxicity in HER2-positive metastatic breast cancer patients. The reduction in ejection fraction was directed at evaluating cardiac toxicity.
Data summary: Fourteen articles evaluated cardiotoxicity as a condition among 2945 individuals, evaluating doxorubicin, epirubicin, Liposomal Doxorubicin (LD), Pegylated Liposomal Doxorubicin (PLD), dexrazoxane plus doxorubicin or epirubicin, and Angiotensin-Converting Enzyme Inhibitors (ACEIs) plus doxorubicin. Pooled Odds Ratio (OR) of 0.043 with a 95% credible interval (CrI) between 0.005 and 0.22 indicated that the dexrazoxane plus epirubicin reduced the number of cardiac events compared with doxorubicin. Furthermore, doxorubicin and epirubicin represented the most effective interventions with a 52% probability of success. Also, the best treatment for reducing Congestive Heart Failure (CHF) was dexrazoxane plus epirubicin with a probability of 43%. For the Left Ventricular Ejection Fraction (LVEF) reduction outcome, ACEIs plus doxorubicin was ranked first with a success probability of 61.2% and they could significantly prevent the reduction in LVEF compared with LD, epirubicin, or doxorubicin.
Conclusion
Our data suggested that angiotensin-converting enzyme inhibitors and dexrazoxane plus epirubicin were the most effective interventions for preventing cardiotoxicity and CHF. However, ACEIs plus doxorubicin was the best treatment for preventing LVEF reduction.
BradshawPTStevensJKhankariN, et al.Cardiovascular disease mortality among breast cancer survivors. Epidemiology (Cambridge, Mass)2016;
27: 6--13.
3.
BoydAStoodleyPRichardsD, et al.Anthracyclines induce early changes in left ventricular systolic and diastolic function: a single centre study. PloS One2017;
12: e0175544.
4.
ZhangSLiuXBawa-KhalfeT, et al.Identification of the molecular basis of doxorubicin-induced cardiotoxicity. Nat Med2012;
18: 1639–1642.
5.
NebigilCGDésaubryLG.Updates in anthracycline-mediated cardiotoxicity. Frontiers in Pharmacology2018;
9: 1262.
6.
ToldoSGoeheRWLotrionteM, et al.Comparative cardiac toxicity of anthracyclines in vitro and in vivo in the mouse. PloS One2013;
8: e58421.
7.
FrancoYLVaidyaTR, A-O.S. Anticancer and cardio-protective effects of liposomal doxorubicin in the treatment of breast cancer. Breast Cancer: Targets Therapy2018;
10: 131.
8.
HasinoffBBPatelDWuX.The oral iron chelator ICL670A (deferasirox) does not protect myocytes against doxorubicin. Free Radic Biol Med2003;
35: 1469–1479
9.
KimmickGDentSKlemI.Risk of cardiomyopathy in breast cancer: how can We attenuate the risk of heart failure from anthracyclines and anti-HER2 therapies?Curr Treat Opt Cardiovasc Med2019;
21: 30.
10.
LiberatiAAltmanDGTetzlaffJ, et al.The PRISMA statement for reporting systematic reviews and Meta-analyses of studies that evaluate health care interventions: explanation and elaboration. PLoS Med2009;
6: e1000100.
11.
HigginsJPAltmanDGGøtzschePC, et al.; Cochrane Statistical Methods Group.
The Cochrane collaboration’s tool for assessing risk of bias in randomised trials. BMJ2011;
343: d5928.
AdesASculpherMSuttonA, et al.Bayesian methods for evidence synthesis in cost-effectiveness analysis. Pharmacoeconomics2006;
24: 1–19.
14.
van ValkenhoefGKuiperJ. GeMTC: network meta-analysis using bayesian methods. R package version 0.8-1. http://github.com/gertvv/gemtc (2016, accessed 23 December 2016).
15.
JansenJPFleurenceRDevineB, et al.Interpreting indirect treatment comparisons and network meta-analysis for health-care decision making: report of the ISPOR task force on indirect treatment comparisons good research practices: part 1. Value Health2011;
14: 417–428.
16.
SalantiGDel GiovaneCChaimaniA, et al.Evaluating the quality of evidence from a network Meta-analysis. PloS One2014;
9: e99682.
17.
DiasSWeltonNCaldwellD, et al.Checking consistency in mixed treatment comparison meta-analysis. Stat Med2010;
29: 932–944.
18.
GelmanARubinDB.Inference from iterative simulation using multiple sequences. Statist Sci1992;
7: 457–472.
19.
JansenJPCrawfordBBergmanG, et al.Bayesian meta-analysis of multiple treatment comparisons: an introduction to mixed treatment comparisons. Value Health2008;
11: 956–964.
20.
SalantiGAdesAIoannidisJP.Graphical methods and numerical summaries for presenting results from multiple-treatment meta-analysis: an overview and tutorial. J Clin Epidemiol2011;
64: 163–171.
21.
AhmedKMcVeighTCerneviciuteR, et al.Effectiveness of contrast-associated acute kidney injury prevention methods; a systematic review and network Meta-analysis. BMC Nephrol2018;
19: 323.
22.
AmbrosiniGBalliMGarusiG, et al.Phase III randomized study of fluorouracil, epirubicin, and cyclophosphamide v fluorouracil, doxorubicin, and cyclophosphamide in advanced breast cancer: an Italian multicentre trial. J Clin Oncol1988;
6: 976–982.
23.
BatistGRamakrishnanGRaoCS, et al.Reduced cardiotoxicity and preserved antitumor efficacy of liposome-encapsulated doxorubicin and cyclophosphamide compared with conventional doxorubicin and cyclophosphamide in a randomized, multicenter trial of metastatic breast cancer. 2001.
19: 1444–1454.
24.
CardinaleDColomboASandriMT, et al.Prevention of high-dose chemotherapy-induced cardiotoxicity in high-risk patients by angiotensin-converting enzyme inhibition. Circulation2006;
114: 2474–2481.
25.
ChanSDavidsonNJuozaityteE, et al.Phase III trial of liposomal doxorubicin and cyclophosphamide compared with epirubicin and cyclophosphamide as first-line therapy for metastatic breast cancer. Ann Oncol2004;
15: 1527–1534.
26.
GroupFES.A prospective randomized phase III trial comparing combination chemotherapy with cyclophosphamide, fluorouracil, and either doxorubicin or epirubicin. J Clin Oncol1988;
6: 679–688.
27.
HarrisLBatistGBeltR, et al.Liposome‐encapsulated doxorubicin compared with conventional doxorubicin in a randomized multicenter trial as first‐line therapy of metastatic breast carcinoma. 2002;
94: 25–36.
28.
HuangGZhaiJHuangX, et al.Predictive value of soluble ST-2 for changes of cardiac function and structure in breast cancer patients receiving chemotherapy. Medicine2018; 97: e12447. DOI: 10.1097/MD.0000000000012447.
29.
JainKCasperEGellerN, et al.A prospective randomized comparison of epirubicin and doxorubicin in patients with advanced breast cancer. J Clin Oncol1985;
3: 818–826.
30.
LopezMViciPDi LauroK, et al.Randomized prospective clinical trial of high-dose epirubicin and dexrazoxane in patients with advanced breast cancer and soft tissue sarcomas. J Clin Oncol1998;
16: 86–92.
31.
MartyMEspieMLlombartA, et al.Multicenter randomized phase III study of the cardioprotective effect of dexrazoxane (cardioxane®) in advanced/metastatic breast cancer patients treated with anthracycline-based chemotherapy. Ann Oncol2006;
17: 614–622.
32.
O'Brien ME, Wigler N, Inbar M, et al. Reduced cardiotoxicity and comparable efficacy in a phase III trial of pegylated liposomal doxorubicin HCl (CAELYX™/Doxil®) versus conventional doxorubicin for first-line treatment of metastatic breast cancer. Annals of Oncology 2004; 15: 440--449.
33.
SpeyerJLGreenMDZeleniuch-JacquotteA, et al.ICRF-187 permits longer treatment with doxorubicin in women with breast cancer. J Clin Oncol1992;
10: 117–127.
34.
SwainSMWhaleyFSGerberMC, et al.Cardioprotection with dexrazoxane for doxorubicin-containing therapy in advanced breast cancer. JCO1997;
15: 1318–1332.
35.
VenturiniMMichelottiADel MastroL, et al.Multicenter randomized controlled clinical trial to evaluate cardioprotection of dexrazoxane versus no cardioprotection in women receiving epirubicin chemotherapy for advanced breast cancer. JCO1996;
14: 3112–3120.
36.
SmithLACorneliusVRPlummerCJ, et al.Cardiotoxicity of anthracycline agents for the treatment of cancer: systematic review and meta-analysis of randomised controlled trials. BMC Cancer2010;
10: 337.
37.
YamaguchiNFujiiTAoiS, et al.Comparison of cardiac events associated with liposomal doxorubicin, epirubicin and doxorubicin in breast cancer: a Bayesian network meta-analysis. Eur J Cancer2015;
51: 2314–2320.
38.
Iqbal M, Dubey K, Anwer T, et al. Protective effects of telmisartan against acute doxorubicin-induced cardiotoxicity in rats. Pharmacological Reports 2008; 60: 382--390.
39.
BlaesADuprezDDeforT, et al.Angiotensin converting enzyme inhibitors (ACEI) and doxorubicin pharmacokinetics in women receiving adjuvant breast cancer treatment. SpringerPlus2015;
4: 32.
40.
Abdel-QadirHOngGFazelzadR, et al.Interventions for preventing cardiomyopathy due to anthracyclines: a Bayesian network meta-analysis. Ann Oncol2017;
28: 628–633.
41.
MaoZShenKZhuL, et al.Comparisons of cardiotoxicity and efficacy of anthracycline-based therapies in breast cancer: a network meta-analysis of randomized clinical trials. Oncol Res Treat2019;
42: 405--413.
