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Emerging cancer therapies and cardiovascular risk

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Abstract

The cardiovascular (CV) toxicity profiles of traditional cancer therapies such as anthracyclines and radiation therapy are familiar to many cardiologists. With the development and widespread use of additional cancer therapeutics, CV toxicities related to these agents are becoming more common. Cardiovascular specialists are often integrated into the care team for individuals with cancer and knowledge of the CV toxicities of cancer therapeutics has become essential. In this review, we provide a clinically focused summary of the current data regarding CV toxicities of common cancer therapies and identify potential management strategies for the CV specialist.

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Fig. 1

(with permission from Hu et al. [3])

Fig. 2
Fig. 3

(with permission from Li et al. [23])

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Abbreviations

ADT:

Androgen deprivation therapy

BP:

Blood pressure

CML:

Chronic myeloid leukemia

CTLA-4:

Cytotoxic T-lymphocyte-associated antigen 4

CV:

Cardiovascular

FDA:

Food and Drug Administration

GnRH:

Gonadotropin releasing receptor hormone

HTN:

Hypertension

ICI:

Immune checkpoint inhibitors

PD-1:

Programmed death -1

PDL-1:

Programmed death ligand- 1

PI:

Proteasome inhibitors

TKI:

Tyrosine kinase inhibitors

VEGFi:

Vascular endothelial growth factor inhibitors

References

  1. Hodi FS et al (2010) Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med 363(8):711–723

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Ribas A (2012) Tumor immunotherapy directed at PD-1. N Engl J Med 366(26):2517–2519

    Article  CAS  PubMed  Google Scholar 

  3. Hu JR et al (2019) Cardiovascular toxicities associated with immune checkpoint inhibitors. Cardiovasc Res 115(5):854–868

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Salem JE et al (2018) Cardiovascular toxicities associated with immune checkpoint inhibitors: an observational, retrospective, pharmacovigilance study. Lancet Oncol 19(12):1579–1589

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Johnson DB et al (2016) Fulminant myocarditis with combination immune checkpoint blockade. N Engl J Med 375(18):1749–1755

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  6. Wang DY et al (2018) Fatal toxic effects associated with immune checkpoint inhibitors: a systematic review and meta-analysis. JAMA Oncol 4(12):1721–1728

    Article  PubMed  PubMed Central  Google Scholar 

  7. Moslehi JJ et al (2018) Increased reporting of fatal immune checkpoint inhibitor-associated myocarditis. Lancet 391(10124):933

    Article  PubMed  PubMed Central  Google Scholar 

  8. Daxini A, Cronin K, Sreih AG (2018) Vasculitis associated with immune checkpoint inhibitors—a systematic review. Clin Rheumatol 37(9):2579–2584

    Article  PubMed  Google Scholar 

  9. Clavijo CS et al (2020) Cardiovascular complications of chimeric antigen receptor T-cell therapy: the cytokine release syndrome and associated arrhythmias. J Immunother Precis Oncol 3(3):113–120

    Article  Google Scholar 

  10. Aldoss I et al (2019) Cytokine release syndrome with the novel treatments of acute lymphoblastic leukemia: pathophysiology, prevention, and treatment. Curr Oncol Rep 21(1):4

    Article  PubMed  Google Scholar 

  11. Linette GP et al (2013) Cardiovascular toxicity and titin cross-reactivity of affinity-enhanced T cells in myeloma and melanoma. Blood 122(6):863–871

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Buckley LF, Abbate A (2018) Interleukin-1 blockade in cardiovascular diseases: a clinical update. Eur Heart J 39(22):2063–2069

    Article  CAS  PubMed  Google Scholar 

  13. Cancer Stat Facts: Kidney and Renal Pelvis Cancer (2019). https://seer.cancer.gov/statfacts/html/kidrp.html. Accessed 5 Jan 2020

  14. Nguyen PL et al (2011) Association of androgen deprivation therapy with cardiovascular death in patients with prostate cancer: a meta-analysis of randomized trials. JAMA 306(21):2359–2366

    Article  CAS  PubMed  Google Scholar 

  15. D’Amico AV et al (2015) Long-term follow-up of a randomized trial of radiation with or without androgen deprivation therapy for localized prostate cancer. JAMA 314(12):1291–1293

    Article  PubMed  Google Scholar 

  16. Gupta D et al (2018) Cardiovascular and metabolic effects of androgen-deprivation therapy for prostate cancer. J Oncol Pract 14(10):580–587

    Article  PubMed  Google Scholar 

  17. Keating NL, O’Malley AJ, Smith MR (2006) Diabetes and cardiovascular disease during androgen deprivation therapy for prostate cancer. J Clin Oncol 24(27):4448–4456

    Article  CAS  PubMed  Google Scholar 

  18. Hu JR et al (2020) Cardiovascular effects of androgen deprivation therapy in prostate cancer: contemporary meta-analyses. Arterioscler Thromb Vasc Biol 40(3):e55–e64

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Shore ND et al (2020) Oral relugolix for androgen-deprivation therapy in advanced prostate cancer. N Engl J Med 382(23):2187–2196

    Article  CAS  PubMed  Google Scholar 

  20. Moreira RB et al (2017) Differential side effects profile in patients with mCRPC treated with abiraterone or enzalutamide: a meta-analysis of randomized controlled trials. Oncotarget 8(48):84572–84578

    Article  PubMed  PubMed Central  Google Scholar 

  21. Iacovelli R et al (2018) The cardiovascular toxicity of abiraterone and enzalutamide in prostate cancer. Clin Genitourin Cancer 16(3):e645–e653

    Article  PubMed  Google Scholar 

  22. Salem JE et al (2019) Androgenic effects on ventricular repolarization: a translational study from the international pharmacovigilance database to iPSC-cardiomyocytes. Circulation 140(13):1070–1080

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Li W et al (2015) Vascular and metabolic implications of novel targeted cancer therapies: focus on kinase inhibitors. J Am Coll Cardiol 66(10):1160–1178

    Article  PubMed  Google Scholar 

  24. Eremina V et al (2008) VEGF inhibition and renal thrombotic microangiopathy. N Engl J Med 358(11):1129–1136

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Lankhorst S et al (2014) Hypertension during vascular endothelial growth factor inhibition: focus on nitric oxide, endothelin-1, and oxidative stress. Antioxid Redox Signal 20(1):135–145

    Article  CAS  PubMed  Google Scholar 

  26. Veronese ML et al (2006) Mechanisms of hypertension associated with BAY 43-9006. J Clin Oncol 24(9):1363–1369

    Article  CAS  PubMed  Google Scholar 

  27. Mourad JJ et al (2008) Blood pressure rise following angiogenesis inhibition by bevacizumab. A crucial role for microcirculation. Ann Oncol 19(5):927–934

    Article  PubMed  Google Scholar 

  28. Belcik JT et al (2012) Cardiovascular and systemic microvascular effects of anti-vascular endothelial growth factor therapy for cancer. J Am Coll Cardiol 60(7):618–625

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Maitland ML et al (2010) Initial assessment, surveillance, and management of blood pressure in patients receiving vascular endothelial growth factor signaling pathway inhibitors. J Natl Cancer Inst 102(9):596–604

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Kerkela R et al (2006) Cardiotoxicity of the cancer therapeutic agent imatinib mesylate. Nat Med 12(8):908–916

    Article  PubMed  CAS  Google Scholar 

  31. Hatfield A, Owen S, Pilot PR (2007) In reply to ‘Cardiotoxicity of the cancer therapeutic agent imatinib mesylate’. Nat Med 13(1):15–16

    Article  CAS  Google Scholar 

  32. Shah NP et al (2016) Dasatinib in imatinib-resistant or -intolerant chronic-phase, chronic myeloid leukemia patients: 7-year follow-up of study CA180-034. Am J Hematol 91(9):869–874

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Hochhaus A et al (2016) Long-term benefits and risks of frontline nilotinib vs imatinib for chronic myeloid leukemia in chronic phase: 5-year update of the randomized ENESTnd trial. Leukemia 30(5):1044–1054

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Cortes JE et al (2018) Ponatinib efficacy and safety in Philadelphia chromosome-positive leukemia: final 5-year results of the phase 2 PACE trial. Blood 132(4):393–404

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Hadzijusufovic E et al (2017) Nilotinib-induced vasculopathy: identification of vascular endothelial cells as a primary target site. Leukemia 31(11):2388–2397

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Pouwer MG et al (2018) The BCR-ABL1 inhibitors imatinib and ponatinib decrease plasma cholesterol and atherosclerosis, and nilotinib and ponatinib activate coagulation in a translational mouse model. Front Cardiovasc Med 5:55

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  37. Manouchehri A et al (2020) Tyrosine kinase inhibitors in leukemia and cardiovascular events: from mechanism to patient care. Arterioscler Thromb Vasc Biol 40(2):301–308

    Article  CAS  PubMed  Google Scholar 

  38. Dimopoulos MA et al (2017) Carfilzomib or bortezomib in relapsed or refractory multiple myeloma (ENDEAVOR): an interim overall survival analysis of an open-label, randomised, phase 3 trial. Lancet Oncol 18(10):1327–1337

    Article  CAS  PubMed  Google Scholar 

  39. Cole DC, Frishman WH (2018) Cardiovascular complications of proteasome inhibitors used in multiple myeloma. Cardiol Rev 26(3):122–129

    Article  PubMed  Google Scholar 

  40. Hasinoff BB, Patel D, Wu X (2017) Molecular mechanisms of the cardiotoxicity of the proteasomal-targeted drugs bortezomib and carfilzomib. Cardiovasc Toxicol 17(3):237–250

    Article  CAS  PubMed  Google Scholar 

  41. Cornell RF et al (2019) Prospective study of cardiac events during proteasome inhibitor therapy for relapsed multiple myeloma. J Clin Oncol 37(22):1946–1955

    Article  CAS  PubMed  Google Scholar 

  42. Chari A, Hajje D (2014) Case series discussion of cardiac and vascular events following carfilzomib treatment: possible mechanism, screening, and monitoring. BMC Cancer 14:915

    Article  PubMed  PubMed Central  Google Scholar 

  43. Chari A et al (2018) Analysis of carfilzomib cardiovascular safety profile across relapsed and/or refractory multiple myeloma clinical trials. Blood Adv 2(13):1633–1644

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Diwadkar S, Patel AA, Fradley MG (2016) Bortezomib-induced complete heart block and myocardial scar: the potential role of cardiac biomarkers in monitoring cardiotoxicity. Case Rep Cardiol 2016:3456287

    PubMed  PubMed Central  Google Scholar 

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Acknowledgements

This publication is supported in part by the To-morrow’s Research Fund St. Baldrick’s Scholar Award (Award Number 636214). The content is solely the responsibility of the authors and does not necessarily represent the official views of St. Baldrick’s Foundation. This publication is supported in part by the American Heart Association (Award Number 19CDA34760181). The content is solely the responsibility of the authors and does not necessarily represent the official views of the American Heart Association.

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Authors and Affiliations

  1. Division of Cardiovascular Medicine, Pauley Heart Center, Department of Internal Medicine, Virginia Commonwealth University, Gateway bldg. 1200 E Marshall St, Richmond, VA, 23298, USA

    Wendy Bottinor

  2. Division of Cardiovascular Medicine, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA

    Wendy Bottinor, Amar Parikh & Eiman Jahangir

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  1. Wendy Bottinor
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  2. Amar Parikh
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  3. Eiman Jahangir
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Correspondence to Wendy Bottinor.

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Bottinor, W., Parikh, A. & Jahangir, E. Emerging cancer therapies and cardiovascular risk. J Thromb Thrombolysis 51, 837–845 (2021). https://doi.org/10.1007/s11239-020-02263-9

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