Độc tính tim mạch của điều trị ung thư vú: bản cập nhật

Cancer Chemotherapy and Pharmacology - Tập 88 - Trang 15-24 - 2021
Christos Papageorgiou1, Angeliki Andrikopoulou1, Meletios-Athanasios Dimopoulos1, Flora Zagouri1
1Department of Clinical Therapeutics, Alexandra General Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece

Tóm tắt

Các tác nhân hóa trị liệu mới đã đánh dấu một kỷ nguyên mới trong ung thư học trong suốt thập kỷ qua, kéo dài đáng kể thời gian sống sót tổng quát của bệnh nhân ung thư vú. Tuy nhiên, các liệu pháp chống ung thư hiện đại thường có thể gây ra các tác dụng phụ trên tim mạch. Những biểu hiện thường gặp của độc tính tim mạch do hóa trị liệu bao gồm bệnh cơ tim, thiếu máu cục bộ, rối loạn dẫn truyền, tăng huyết áp và các sự kiện huyết khối - tắc mạch, trong khi loại chế độ điều trị được áp dụng quyết định quan trọng đến kết quả lâm sàng. Mục tiêu của bài tổng quan tài liệu này là phân tích tỷ lệ mắc và các cơ chế tiềm ẩn của độc tính tim mạch do các tác nhân được phê duyệt cho ung thư vú, cũng như mô tả các phương pháp theo dõi và điều trị các tác dụng độc tính tim mạch ở bệnh nhân ung thư vú. Hơn nữa, nghiên cứu của chúng tôi nhằm cung cấp một cái nhìn dễ hiểu về những tiến bộ gần đây và có ý nghĩa lâm sàng trong lĩnh vực này.

Từ khóa

#độc tính tim mạch #hóa trị liệu #ung thư vú #tác dụng phụ #theo dõi và điều trị

Tài liệu tham khảo

Thomas M, Suter MSE (2013) Cancer drugs and the heart: importance and management. Eur Hear J 34(15):1102–1111 Ewer MS, Suter TM, Lenihan DJ et al (2014) Cardiovascular events among 1090 cancer patients treated with sunitinib, interferon, or placebo: a comprehensive adjudicated database analysis demonstrating clinically meaningful reversibility of cardiac events. Eur J Cancer 50:2162–2170. https://doi.org/10.1016/j.ejca.2014.05.013 ESC guidelines—cancer treatments & cardiovascular toxicity (2016 ESC position paper). https://www.escardio.org/Guidelines/Clinical-Practice-Guidelines/cancer-treatments-cardiovascular-toxicity-2016-position-paper. Accessed 3 July 2020 Cardinale D, Colombo A, Bacchiani G et al (2015) Early detection of anthracycline cardiotoxicity and improvement with heart failure therapy. Circulation 131:1981–1988. https://doi.org/10.1161/CIRCULATIONAHA.114.013777 Volkova M, Russell R (2012) Anthracycline cardiotoxicity: prevalence, pathogenesis and treatment. Curr Cardiol Rev 7:214–220. https://doi.org/10.2174/157340311799960645 Fernandez SF, Basra M, Canty JM (2011) Takotsubo cardiomyopathy following initial chemotherapy presenting with syncope and cardiogenic shock—a case report and literature review. J Clinic Experiment Cardiol 2:2. https://doi.org/10.4172/2155-9880.1000124 MM H, SS L, J C et al (1985) Doxorubicin-induced congestive heart failure in adults. Cancer.https://doi.org/10.1002/1097-0142(19850915)56:6<1361::AID-CNCR2820560624>3.0.CO;2-S Groarke JD, Nohria A (2015) Editorial: Anthracycline cardiotoxicity a new paradigm for an old classic. Circulation 131:1946–1949 Corremans R, Adão R, De Keulenaer GW et al (2019) Update on pathophysiology and preventive strategies of anthracycline-induced cardiotoxicity. Clin Exp Pharmacol Physiol 46:204–215 Narayan HK, Finkelman B, French B et al (2017) Detailed echocardiographic phenotyping in breast cancer patients: associations with ejection fraction decline, recovery, and heart failure symptoms over 3 years of follow-up. Circulation 135:1397–1412. https://doi.org/10.1161/CIRCULATIONAHA.116.023463 Serrano JM, González I, Del Castillo S et al (2015) Diastolic dysfunction following anthracycline-based chemotherapy in breast cancer patients: incidence and predictors. Oncologist 20:864–872. https://doi.org/10.1634/theoncologist.2014-0500 Arbuck SG, Strauss H, Rowinsky E, Christian M, Suffness M, Adams J, Oakes M, McGuire W, Reed E, Gibbs H et al (1993) A reassessment of cardiac toxicity associated with taxol—PubMed. J Natl Cancer Inst Monogr (15):117–130 Rowinsky EK, McGuire WP, Guarnieri T et al (1991) Cardiac disturbances during the administration of taxol. J Clin Oncol 9:1704–1712. https://doi.org/10.1200/JCO.1991.9.9.1704 Madeddu C, Deidda M, Piras A et al (2016) Pathophysiology of cardiotoxicity induced by nonanthracycline chemotherapy. J Cardiovasc Med 17:S12–S18. https://doi.org/10.2459/JCM.0000000000000376 Castel M, Despas F, Modesto A et al (2013) Effets indésirables cardiaques des chimiothérapies. Press Medicale 42:26–39 Curigliano G, 1 DCTSGPE de AMTSCCAGCCFREGWG (2012) Cardiovascular toxicity induced by chemotherapy, targeted agents and radiotherapy: ESMO clinical practice guidelines—PubMed. https://pubmed.ncbi.nlm.nih.gov/22997448/. Accessed 3 Jul 2020 Polk A, Vistisen K, Vaage-Nilsen M, Nielsen DL (2014) A systematic review of the pathophysiology of 5-fluorouracil-induced cardiotoxicity. BMC Pharmacol Toxicol 15:47. https://doi.org/10.1186/2050-6511-15-47 Polk A, Vaage-Nilsen M, Vistisen K, Nielsen DL (2013) Cardiotoxicity in cancer patients treated with 5-fluorouracil or capecitabine: a systematic review of incidence, manifestations and predisposing factors. Cancer Treat Rev 39:974–984 Chong JH, Ghosh AK (2019) Coronary artery vasospasm induced by 5-fluorouracil: proposed mechanisms, existing management options and future directions. Interv Cardiol Rev 14:89–94. https://doi.org/10.15420/icr.2019.12 Polk A, Shahmarvand N, Vistisen K et al (2016) Incidence and risk factors for capecitabine-induced symptomatic cardiotoxicity: a retrospective study of 452 consecutive patients with metastatic breast cancer. BMJ Open. https://doi.org/10.1136/bmjopen-2016-012798 Kosmas C, Kallistratos MS, Kopterides P et al (2008) Cardiotoxicity of fluoropyrimidines in different schedules of administration: a prospective study. J Cancer Res Clin Oncol 134:75–82. https://doi.org/10.1007/s00432-007-0250-9 Sara JD, Kaur J, Khodadadi R et al (2018) 5-fluorouracil and cardiotoxicity: a review. Ther Adv Med Oncol 10:1758835918780140. https://doi.org/10.1177/1758835918780140 Lapeyre-Mestre M, Gregoire N, Bugat R, Montastruc J-L (2004) Vinorelbine-related cardiac events: a meta-analysis of randomized clinical trials. Fundam Clin Pharmacol 18:97–105. https://doi.org/10.1046/j.0767-3981.2003.00215.x Lorusso V, Giota F, Bordonaro R et al (2014) Non-pegylated liposome-encapsulated doxorubicin citrate plus cyclophosphamide or vinorelbine in metastatic breast cancer not previously treated with chemotherapy: a multicenter phase III study. Int J Oncol 45:2137–2142. https://doi.org/10.3892/ijo.2014.2604 Braverman AC, Antin JH, Plappert MT et al (1991) Cyclophosphamide cardiotoxicity in bone marrow transplantation: a prospective evaluation of new dosing regimens. J Clin Oncol 9:1215–1223. https://doi.org/10.1200/JCO.1991.9.7.1215 Ayza MA, Zewdie KA, Tesfaye BA et al (2020) The role of antioxidants in ameliorating cyclophosphamide-induced cardiotoxicity. Oxid Med Cell Longev. https://doi.org/10.1155/2020/4965171 Cameron D, Piccart-Gebhart MJ, Gelber RD et al (2017) 11 years’ follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive early breast cancer: final analysis of the HERceptin Adjuvant (HERA) trial. Lancet 389:1195–1205. https://doi.org/10.1016/S0140-6736(16)32616-2 Romond EH, Perez EA, Bryant J et al (2005) Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med 353:1673–1684. https://doi.org/10.1056/NEJMoa052122 Slamon DJ, Leyland-Jones B, Shak S et al (2001) Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med 344:783–792. https://doi.org/10.1056/NEJM200103153441101 Kotwinski P, Smith G, Cooper J et al (2016) Body surface area and baseline blood pressure predict subclinical anthracycline cardiotoxicity in women treated for early breast cancer. PLoS ONE. https://doi.org/10.1371/journal.pone.0165262 Finkelman BS, Putt M, Wang T et al (2017) Arginine-nitric oxide metabolites and cardiac dysfunction in patients with breast cancer. J Am Coll Cardiol 70:152–162. https://doi.org/10.1016/j.jacc.2017.05.019 Sawaya H, Sebag IA, Plana JC et al (2012) Assessment of echocardiography and biomarkers for the extended prediction of cardiotoxicity in patients treated with anthracyclines, taxanes, and trastuzumab. Circ Cardiovasc Imaging 5:596–603. https://doi.org/10.1161/CIRCIMAGING.112.973321 De Azambuja E, Procter MJ, Van Veldhuisen DJ et al (2014) Trastuzumab-associated cardiac events at 8 years of median follow-up in the herceptin adjuvant trial (BIG 1–01). J Clin Oncol 32:2159–2165. https://doi.org/10.1200/JCO.2013.53.9288 Thavendiranathan P, Poulin F, Lim KD et al (2014) Use of myocardial strain imaging by echocardiography for the early detection of cardiotoxicity in patients during and after cancer chemotherapy: a systematic review. J Am Coll Cardiol 63:2751–2768 Cardinale D, Colombo A, Torrisi R et al (2010) Trastuzumab-induced cardiotoxicity: clinical and prognostic implications of troponin I evaluation. J Clin Oncol 28:3910–3916. https://doi.org/10.1200/JCO.2009.27.3615 Jones AL, Barlow M, Barrett-Lee PJ et al (2009) Management of cardiac health in trastuzumab-treated patients with breast cancer: updated United Kingdom National Cancer Research Institute recommendations for monitoring. Br J Cancer 100:684–692. https://doi.org/10.1038/sj.bjc.6604909 Geyer CE, Forster J, Lindquist D et al (2006) Lapatinib plus capecitabine for HER2-positive advanced breast cancer. N Engl J Med 355:2733–2743. https://doi.org/10.1056/NEJMoa064320 Cameron D, Casey M, Press M et al (2008) A phase III randomized comparison of lapatinib plus capecitabine versus capecitabine alone in women with advanced breast cancer that has progressed on trastuzumab: updated efficacy and biomarker analyses. Breast Cancer Res Treat 112:533–543. https://doi.org/10.1007/s10549-007-9885-0 Piccart-Gebhart M, Holmes E, Baselga J et al (2016) Adjuvant lapatinib and trastuzumab for early human epidermal growth factor receptor 2-positive breast cancer: results from the randomized phase III adjuvant lapatinib and/or trastuzumab treatment optimization trial. J Clin Oncol 34:1034–1042. https://doi.org/10.1200/JCO.2015.62.1797 Perez EA, Koehler M, Byrne J et al (2008) Cardiac safety of lapatinib: pooled analysis of 3689 patients enrolled in clinical trials. Mayo Clin Proc 83:679–686. https://doi.org/10.4065/83.6.679 Baselga J, Cortés J, Kim S-B et al (2012) Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer. N Engl J Med 366:109–119. https://doi.org/10.1056/NEJMoa1113216 Verma S, Miles D, Gianni L et al (2012) Trastuzumab emtansine for HER2-positive advanced breast cancer. N Engl J Med 367:1783–1791. https://doi.org/10.1056/NEJMoa1209124 Von Minckwitz G, Huang CS, Mano MS et al (2019) Trastuzumab emtansine for residual invasive HER2-positive breast cancer. N Engl J Med 380:617–628. https://doi.org/10.1056/NEJMoa1814017 Peddi PF, Hurvitz SA (2014) Ado-trastuzumab emtansine (T-DM1) in human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer: latest evidence and clinical potential. Ther Adv Med Oncol 6:202–209 Perez EA, Barrios C, Eiermann W et al (2017) Trastuzumab emtansine with or without pertuzumab versus trastuzumab plus taxane for human epidermal growth factor receptor 2-positive, advanced breast cancer: primary results from the phase III MARIANNE study. J Clin Oncol 35:141–148. https://doi.org/10.1200/JCO.2016.67.4887 Modi S, Saura C, Yamashita T et al (2020) Trastuzumab deruxtecan in previously treated HER2-positive breast cancer. N Engl J Med 382:610–621. https://doi.org/10.1056/NEJMoa1914510 Tamura K, Tsurutani J, Takahashi S et al (2019) Trastuzumab deruxtecan (DS-8201a)in patients with advanced HER2-positive breast cancer previously treated with trastuzumab emtansine: a dose-expansion, phase 1 study. Lancet Oncol 20:816–826. https://doi.org/10.1016/S1470-2045(19)30097-X Burstein HJ, Sun Y, Dirix LY et al (2010) Neratinib, an irreversible ErbB receptor tyrosine kinase inhibitor, in patients with advanced ErbB2-positive breast cancer. J Clin Oncol 28:1301–1307. https://doi.org/10.1200/JCO.2009.25.8707 A study of neratinib plus capecitabine versus lapatinib plus capecitabine in patients with HER2+ metastatic breast cancer who have received two or more prior HER2 directed regimens in the metastatic setting—study results—ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/results/NCT01808573?view=results NCT01808573 Yoshinori I, 1 MSKHSTMYYOKYSHKHHHNTNB (2012) Safety, efficacy and pharmacokinetics of neratinib (HKI-272) in Japanese patients with advanced solid tumors: a phase 1 dose-escalation study—PubMed. https://pubmed.ncbi.nlm.nih.gov/22371427/. Accessed 3 July 2020 Lin NU, Winer EP, Wheatley D et al (2012) A phase II study of afatinib (BIBW 2992), an irreversible ErbB family blocker, in patients with HER2-positive metastatic breast cancer progressing after trastuzumab. Breast Cancer Res Treat 133:1057–1065. https://doi.org/10.1007/s10549-012-2003-y Sahebkar A, Serban MC, Penson P et al (2017) The effects of tamoxifen on plasma lipoprotein(a) concentrations: systematic review and meta-analysis. Drugs 77:1187–1197 Howell A, Cuzick J, Baum M, Buzdar A, Dowsett M, Forbes JF, Hoctin-Boes G, Houghton J, Locker GY, Tobias JS, ATAC Trialists' Group (2005) Results of the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial after completion of 5 years’ adjuvant treatment for breast cancer. Lancet 365(9453):60–62. https://doi.org/10.1016/S0140-6736(04)17666-6 Van De Velde CJ, Rea D, Seynaeve C et al (2011) Adjuvant tamoxifen and exemestane in early breast cancer (TEAM): a randomised phase 3 trial. Lancet 377:321–331. https://doi.org/10.1016/S0140-6736(10)62312-4 Regan MM, Price KN, Giobbie-Hurder A et al (2011) Interpreting breast international group (BIG) 1–98: a randomized, double-blind, phase III trial comparing letrozole and tamoxifen as adjuvant endocrine therapy for postmenopausal women with hormone receptor-positive, early breast cancer. Breast Cancer Res 13(3):209. https://doi.org/10.1186/bcr2837 Khosrow-Khavar F, NBKBFSSLA (2020) Cardiotoxicity of sequential aromatase inhibitors use in women with breast cancer. Am J Epidemiol. https://doi.org/10.1093/aje/kwaa065/5824922?redirectedFrom=fulltext Grouthier V, Lebrun-Vignes B, Glazer AM et al (2018) Increased long QT and torsade de pointes reporting on tamoxifen compared with aromatase inhibitors. Heart. https://doi.org/10.1136/heartjnl-2017-312934 Markopoulos CJ, Tsaroucha AK, Gogas HJ (2010) Effect of aromatase inhibitors on the lipid profile of postmenopausal breast cancer patients. Clin Lipidol 5:245–254 Di Leo A, Jerusalem G, Petruzelka L, Torres R et al (2014) Final overall survival: fulvestrant 500 mg vs 250 mg in therandomized CONFIRM trial. J Natl Cancer Inst 106(1):djt337. https://doi.org/10.1093/jnci/djt337. Howell A, Robertson JFR, Abram P et al (2004) Comparison of fulvestrant versus tamoxifen for the treatment of advanced breast cancer in postmenopausal women previously untreated with endocrine therapy: a multinational, double-blind, randomized trial. J Clin Oncol 22:1605–1613. https://doi.org/10.1200/JCO.2004.02.112 Chia S, Gradishar W, Mauriac L et al (2008) Double-blind, randomized placebo controlled trial of fulvestrant compared with exemestane after prior nonsteroidal aromatase inhibitor therapy in postmenopausal women with hormone receptor-positive, advanced breast cancer: Rsults from EFECT. J Clin Oncol 26:1664–1670. https://doi.org/10.1200/JCO.2007.13.5822 Bjornsti MA, Houghton PJ (2004) The TOR pathway: A target for cancer therapy. Nat Rev Cancer 4:335–348 Rugo HS, Pritchard KI, Gnant M, Noguchi S, Piccart M, Hortobagyi G et al (2014) Incidence and time course of everolimus-related adverse events in postmenopausal women with hormone receptor-positive advanced breast cancer: insights from BOLERO-2. Ann Oncol 25(4):808–815 Wolff AC, Lazar AA, Bondarenko I et al (2013) Randomized phase III placebo-controlled trial of letrozole plus oral temsirolimus as first-line endocrine therapy in postmenopausal women with locally advanced or metastatic breast cancer. J Clin Oncol 31:196–202. https://doi.org/10.1200/JCO.2011.38.3331 André F, O’Regan R, Ozguroglu M et al (2014) Everolimus for women with trastuzumab-resistant, HER2-positive, advanced breast cancer (BOLERO-3): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet Oncol 15:580–591. https://doi.org/10.1016/S1470-2045(14)70138-X Updated results from MONALEESA-2, a phase III trial of first-line ribociclib plus letrozole versus placebo plus letrozole in hormone receptor-positive, HER2-negative advanced breast cancer. Ann Oncol. https://www.annalsofoncology.org/article/S0923-7534(19)32105-2/fulltext. Accessed 3 July 2020 Slamon DJ, Neven P, Chia S et al (2018) Phase III randomized study of ribociclib and fulvestrant in hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer: MONALEESA-3. J Clin Oncol 36:2465–2472. https://doi.org/10.1200/JCO.2018.78.9909 Tripathy D, Im SA, Colleoni M et al (2018) Ribociclib plus endocrine therapy for premenopausal women with hormone-receptor-positive, advanced breast cancer (MONALEESA-7): a randomised phase 3 trial. Lancet Oncol 19:904–915. https://doi.org/10.1016/S1470-2045(18)30292-4 Verma S, Bartlett CH, Schnell P et al (2016) Palbociclib in combination with fulvestrant in women with hormone receptor-positive/HER2-negative advanced metastatic breast cancer: detailed safety analysis from a multicenter, randomized, placebo-controlled, phase III study (PALOMA-3). Oncologist 21:1165–1175. https://doi.org/10.1634/theoncologist.2016-0097 André F, Ciruelos E, Rubovszky G et al (2019) Alpelisib for PIK3CA -mutated, hormone receptor-positive advanced breast cancer. N Engl J Med 380:1929–1940. https://doi.org/10.1056/NEJMoa1813904 Yang T, Meoli DF, Moslehi J, Roden DM (2018) Inhibition of the a-subunit of phosphoinositide 3-kinase in heart increases late sodium current and is arrhythmogenic. J Pharmacol Exp Ther 365:460–466. https://doi.org/10.1124/jpet.117.246157 Chang WT, Feng YH, Kuo YH et al (2020) Layer-specific distribution of myocardial deformation from anthracycline-induced cardiotoxicity in patients with breast cancer—from bedside to bench. Int J Cardiol 311:64–70. https://doi.org/10.1016/j.ijcard.2020.01.036 Anastasiou M, Oikonomou E, Zagouri F et al (2017) Flow-mediated dilation of brachial artery as a screening tool for anthracycline-induced cardiotoxicity. J Am Coll Cardiol 70:3072 Kitayama H, Kondo T, Sugiyama J et al (2017) High-sensitive troponin T assay can predict anthracycline- and trastuzumab-induced cardiotoxicity in breast cancer patients. Breast Cancer 24:774–782. https://doi.org/10.1007/s12282-017-0778-8 Left ventricular systolic dysfunction predicted by early troponin I release after anthracycline based chemotherapy in breast cancer patients. PubMed. https://pubmed.ncbi.nlm.nih.gov/28718245/. Accessed 3 July 2020 Maisel AS, Koon J, Krishnaswamy P et al (2001) Utility of B-natriuretic peptide as a rapid, point-of-care test for screening patients undergoing echocardiography to determine left ventricular dysfunction. Am Heart J 141:367–374. https://doi.org/10.1067/mhj.2001.113215 Meinardi MT, Van Veldhuisen DJ, Gietema JA et al (2001) Prospective evaluation of early cardiac damage induced by epirubicin-containing adjuvant chemotherapy and locoregional radiotherapy in breast cancer patients. J Clin Oncol 19:2746–2753. https://doi.org/10.1200/JCO.2001.19.10.2746 Lu X, Zhao Y, Chen C et al (2019) BNP as a marker for early prediction of anthracycline-induced cardiotoxicity in patients with breast cancer. Oncol Lett 18:4992–5001. https://doi.org/10.3892/ol.2019.10827 Van Boxtel W, Bulten BF, Mavinkurve-Groothuis AMC et al (2015) New biomarkers for early detection of cardiotoxicity after treatment with docetaxel, doxorubicin and cyclophosphamide. Biomarkers 20:143–148. https://doi.org/10.3109/1354750X.2015.1040839 Rigaud VOC, Ferreira LRP, Ayub-Ferreira SM et al (2017) Circulating miR-1 as a potential biomarker of doxorubicininduced cardiotoxicity in breast cancer patients. Oncotarget 8:6994–7002. https://doi.org/10.18632/oncotarget.14355 Leger KJ, Leonard D, Nielson D et al (2017) Circulating microRNAs: potential markers of cardiotoxicity in children and young adults treated with anthracycline chemotherapy. J Am Heart Assoc. https://doi.org/10.1161/JAHA.116.004653 Daniela Cardinale FICMC (2020) Cardiotoxicity of anthracyclines—PubMed. Front Cardiovasc Med 7:26. https://doi.org/10.3389/fcvm.2020.00026 Swain SM, Whaley FS, Gerber MC et al (1997) Delayed administration of dexrazoxane provides cordiaprotection for patients with advanced breast cancer treated with doxorubicin-containing therapy. J Clin Oncol 15:1333–1340. https://doi.org/10.1200/JCO.1997.15.4.1333 FDA, CDER Zinecard® (dexrazoxane for injection) Bosch X, Rovira M, Sitges M et al (2013) Enalapril and carvedilol for preventing chemotherapy-induced left ventricular systolic dysfunction in patients with malignant hemopathies. J Am Coll Cardiol 61:2355–2362. https://doi.org/10.1016/j.jacc.2013.02.072 Geeta G, Siri LH, Anne HR et al (2016) Prevention of cardiac dysfunction during adjuvant breast cancer therapy (PRADA): a 2 × 2 factorial, randomized, placebo-controlled, double-blind clinical trial of candesartan and metoprolol—PubMed. Eur Hear. J 37(21):1671–1680. https://doi.org/10.1093/eurheartj/ehw022 Avila MS, Ayub-Ferreira SM, de Barros Wanderley MR et al (2018) Carvedilol for prevention of chemotherapy-related cardiotoxicity: the CECCY trial. J Am Coll Cardiol 71:2281–2290. https://doi.org/10.1016/j.jacc.2018.02.049