Skip to main content

Advertisement

SpringerLink
Log in

Cardiovascular Complications of Prostate Cancer Therapy

  • Cardio-oncology (M Fradley, Section Editor)
  • Published:
Current Treatment Options in Cardiovascular Medicine Aims and scope Submit manuscript

Abstract

Purpose of review

With treatment advances, the most common cause of death in prostate cancer patients is cardiovascular disease. Discerning the contribution of prostate cancer treatment on cardiovascular complications versus the natural progression of cardiovascular disease remains an ongoing area of investigation. Evaluating the research and identifying opportunities for further investigation is critical for optimal care of this prostate cancer patient population.

Recent findings

The degree that hormone therapy contributes to cardiovascular morbidity and mortality remains uncertain with conflicting results from large meta-analyses. Underlying cardiovascular disease or multiple cardiovascular disease risk factors appear to compound the risk of adverse events. Drug-specific cardiotoxicity in prostate cancer treatment has not been fully delineated. Recent studies have suggested the potential for wide-ranging prostate cancer cardiotoxic effects, including atherosclerosis acceleration, myocardial infarction, cardiomyopathy, hypertension, arrhythmias, and stroke along with other thromboembolic diseases.

Summary

This review provides an overview of prostate cancer treatment, a comprehensive analysis of the literature linking androgen deprivation therapy and cardiovascular disease, a discussion of cardiovascular risk management and mitigation in prostate cancer patients, and an exploration of research opportunities within cardio-oncology for prostate cancer.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References and Recommended Reading

  1. Howlader N, Noone AM, Krapcho M, Miller D, Brest A, Yu M, et al., editors. SEER cancer statistics review, 1975–2017. Bethesda: National Cancer Institute. https://seer.cancer.gov/csr/1975_2017/. Based on November 2019 SEER data submission, posted to the SEER web site, April 2020.

  2. Hamdy FC, Donovan JL, Lane JA, Mason M, Metcalfe C, Holding P, et al. 10-year outcomes after monitoring, surgery, or radiotherapy for localized prostate cancer. N Engl J Med. 2016;375:1415–24.

    PubMed  Google Scholar 

  3. Bolla M, Van Tienhoven G, Warde P, Dubois JB, Mirimanoff RO, Storme G, et al. External irradiation with or without long-term androgen suppression for prostate cancer with high metastatic risk: 10-year results of an EORTC randomised study. Lancet Oncol. 2010;11:1066–73.

    CAS  PubMed  Google Scholar 

  4. Denham JW, Steigler A, Lamb DS, Joseph D, Turner S, Matthews J, et al. Short-term neoadjuvant androgen deprivation and radiotherapy for locally advanced prostate cancer: 10-year data from the TROG 96.01 randomised trial. Lancet Oncol. 2011;12:451–9.

    CAS  PubMed  Google Scholar 

  5. Horwitz EM, Bae K, Hanks GE, Porter A, Grignon DJ, Brereton HD, et al. Ten-year follow-up of radiation therapy oncology group protocol 92-02: a phase III trial of the duration of elective androgen deprivation in locally advanced prostate cancer. J Clin Oncol. 2008;26:2497–504.

    CAS  PubMed  Google Scholar 

  6. Platz EA, Till C, Goodman PJ, Parnes HL, Figg WD, Albanes D, et al. Men with low serum cholesterol have a lower risk of high-grade prostate cancer in the placebo arm of the prostate cancer prevention trial. Cancer Epidemiol Biomark Prev. 2009;18:2807–13.

    CAS  Google Scholar 

  7. Platz EA, Clinton SK, Giovannucci E. Association between plasma cholesterol and prostate cancer in the PSA era. Int J Cancer. 2008;123:1693–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Cao Y, Ma J. Body mass index, prostate cancer-specific mortality, and biochemical recurrence: a systematic review and meta-analysis. Cancer Prev Res (Phila). 2011;4:486–501.

    CAS  Google Scholar 

  9. Discacciati A, Orsini N, Wolk A. Body mass index and incidence of localized and advanced prostate cancer--a dose-response meta-analysis of prospective studies. Ann Oncol. 2012;23:1665–71.

    CAS  PubMed  Google Scholar 

  10. Huncharek M, Haddock KS, Reid R, Kupelnick B. Smoking as a risk factor for prostate cancer: a meta-analysis of 24 prospective cohort studies. Am J Public Health. 2010;100:693–701.

    PubMed  PubMed Central  Google Scholar 

  11. Davis MK, Rajala JL, Tyldesley S, Pickles T, Virani SA. The prevalence of cardiac risk factors in men with localized prostate cancer undergoing androgen deprivation therapy in British Columbia, Canada. J Oncol. 2015;2015:820403.

    PubMed  PubMed Central  Google Scholar 

  12. Litwin MS, Tan HJ. The diagnosis and treatment of prostate cancer: a review. Jama. 2017;317:2532–42.

    PubMed  Google Scholar 

  13. Wang H, Wallner K, Sutlief S, Blasko J, Russell K, Ellis W. Transperineal brachytherapy in patients with large prostate glands. Int J Cancer. 2000;90:199–205.

    CAS  PubMed  Google Scholar 

  14. Sartor O, de Bono JS. Metastatic prostate cancer. N Engl J Med. 2018;378:645–57.

    CAS  PubMed  Google Scholar 

  15. Klotz L, O’Callaghan C, Ding K, Toren P, Dearnaley D, Higano CS, et al. Nadir testosterone within first year of androgen-deprivation therapy (ADT) predicts for time to castration-resistant progression: a secondary analysis of the PR-7 trial of intermittent versus continuous ADT. J Clin Oncol. 2015;33:1151–6.

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Crawford ED, Heidenreich A, Lawrentschuk N, Tombal B, Pompeo ACL, Mendoza-Valdes A, et al. Androgen-targeted therapy in men with prostate cancer: evolving practice and future considerations. Prostate Cancer Prostatic Dis. 2019;22:24–38.

    PubMed  Google Scholar 

  17. Shore ND, Saad F, Cookson MS, George DJ, Saltzstein DR, Tutrone R, et al. Oral relugolix for androgen-deprivation therapy in advanced prostate cancer. N Engl J Med. 2020;382:2187–96.

    CAS  PubMed  Google Scholar 

  18. Beer TM, Armstrong AJ, Rathkopf DE, Loriot Y, Sternberg CN, Higano CS, et al. Enzalutamide in metastatic prostate cancer before chemotherapy. N Engl J Med. 2014;371:424–33.

    PubMed  PubMed Central  Google Scholar 

  19. Scher HI, Fizazi K, Saad F, Taplin ME, Sternberg CN, Miller K, et al. Increased survival with enzalutamide in prostate cancer after chemotherapy. N Engl J Med. 2012;367:1187–97.

    CAS  PubMed  Google Scholar 

  20. Smith MR, Saad F, Chowdhury S, Oudard S, Hadaschik BA, Graff JN, et al. Apalutamide treatment and metastasis-free survival in prostate Cancer. N Engl J Med. 2018;378:1408–18.

    CAS  PubMed  Google Scholar 

  21. Fizazi K, Shore N, Tammela TL, Ulys A, Vjaters E, Polyakov S, et al. Darolutamide in nonmetastatic, castration-resistant prostate cancer. N Engl J Med. 2019;380:1235–46.

    CAS  PubMed  Google Scholar 

  22. de Bono JS, Logothetis CJ, Molina A, Fizazi K, North S, Chu L, et al. Abiraterone and increased survival in metastatic prostate cancer. N Engl J Med. 2011;364:1995–2005.

    PubMed  PubMed Central  Google Scholar 

  23. Ryan CJ, Smith MR, de Bono JS, Molina A, Logothetis CJ, de Souza P, et al. Abiraterone in metastatic prostate cancer without previous chemotherapy. N Engl J Med. 2013;368:138–48.

    CAS  PubMed  Google Scholar 

  24. Levine GN, D’Amico AV, Berger P, Clark PE, Eckel RH, Keating NL, et al. Androgen-deprivation therapy in prostate cancer and cardiovascular risk: a science advisory from the American Heart Association, American Cancer Society, and American Urological Association: endorsed by the American Society for Radiation Oncology. Circulation. 2010;121:833–40.

    PubMed  PubMed Central  Google Scholar 

  25. Alibhai SM, Duong-Hua M, Sutradhar R, Fleshner NE, Warde P, Cheung AM, et al. Impact of androgen deprivation therapy on cardiovascular disease and diabetes. J Clin Oncol. 2009;27:3452–8.

    PubMed  Google Scholar 

  26. Van Hemelrijck M, Garmo H, Holmberg L, Ingelsson E, Bratt O, Bill-Axelson A, et al. Absolute and relative risk of cardiovascular disease in men with prostate cancer: results from the population-based PCBaSe Sweden. J Clin Oncol. 2010;28:3448–56.

    PubMed  Google Scholar 

  27. Smith MR, Klotz L, Persson BE, Olesen TK, Wilde AA. Cardiovascular safety of degarelix: results from a 12-month, comparative, randomized, open label, parallel group phase III trial in patients with prostate cancer. J Urol. 2010;184:2313–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Carneiro A, Sasse AD, Wagner AA, Peixoto G, Kataguiri A, Neto AS, et al. Cardiovascular events associated with androgen deprivation therapy in patients with prostate cancer: a systematic review and meta-analysis. World J Urol. 2015;33:1281–9.

    CAS  PubMed  Google Scholar 

  29. O'Farrell S, Garmo H, Holmberg L, Adolfsson J, Stattin P, Van Hemelrijck M. Risk and timing of cardiovascular disease after androgen-deprivation therapy in men with prostate cancer. J Clin Oncol. 2015;33:1243–51.

    CAS  PubMed  Google Scholar 

  30. Lester-Coll NH, Goldhaber SZ, Sher DJ, D'Amico AV. Death from high-risk prostate cancer versus cardiovascular mortality with hormonal therapy: a decision analysis. Cancer. 2013;119:1808–15.

    PubMed  Google Scholar 

  31. Gagliano-Juca T, Travison TG, Kantoff PW, Nguyen PL, Taplin ME, Kibel AS, et al. Androgen deprivation therapy is associated with prolongation of QTc interval in men with prostate cancer. J Endocr Soc. 2018;2:485–96.

    CAS  PubMed  PubMed Central  Google Scholar 

  32. Salem JE, Yang T, Moslehi JJ, Waintraub X, Gandjbakhch E, Bachelot A, et al. Androgenic effects on ventricular repolarization: a translational study from the International Pharmacovigilance Database to iPSC-Cardiomyocytes. Circulation. 2019;140:1070–80.

    CAS  PubMed  PubMed Central  Google Scholar 

  33. Keating NL, O'Malley AJ, Smith MR. Diabetes and cardiovascular disease during androgen deprivation therapy for prostate cancer. J Clin Oncol. 2006;24:4448–56.

    CAS  PubMed  Google Scholar 

  34. Saigal CS, Gore JL, Krupski TL, Hanley J, Schonlau M, Litwin MS. Androgen deprivation therapy increases cardiovascular morbidity in men with prostate cancer. Cancer. 2007;110:1493–500.

    CAS  PubMed  Google Scholar 

  35. Keating NL, O’Malley AJ, Freedland SJ, Smith MR. Diabetes and cardiovascular disease during androgen deprivation therapy: observational study of veterans with prostate cancer. J Natl Cancer Inst. 2010;102:39–46.

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Zhao J, Zhu S, Sun L, Meng F, Zhao L, Zhao Y, et al. Androgen deprivation therapy for prostate cancer is associated with cardiovascular morbidity and mortality: a meta-analysis of population-based observational studies. PLoS One. 2014;9:e107516.

    PubMed  PubMed Central  Google Scholar 

  37. Nguyen PL, Je Y, Schutz FA, Hoffman KE, Hu JC, Parekh A, et al. Association of androgen deprivation therapy with cardiovascular death in patients with prostate cancer: a meta-analysis of randomized trials. JAMA. 2011;306:2359–66.

    CAS  PubMed  Google Scholar 

  38. Bonsu JM, Guha A, Charles L, Yildiz VO, Wei L, Baker B, et al. Reporting of cardiovascular events in clinical trials supporting FDA approval of contemporary cancer therapies. J Am Coll Cardiol. 2020;75:620–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  39. Di Nunno V, Mollica V, Santoni M, Gatto L, Schiavina R, Fiorentino M, et al. New hormonal agents in patients with nonmetastatic castration-resistant prostate cancer: meta-analysis of efficacy and safety outcomes. Clin Genitourin Cancer. 2019;17:e871–7.

    PubMed  Google Scholar 

  40. Efstathiou JA, Bae K, Shipley WU, Hanks GE, Pilepich MV, Sandler HM, et al. Cardiovascular mortality after androgen deprivation therapy for locally advanced prostate cancer: RTOG 85-31. J Clin Oncol. 2009;27:92–9.

    PubMed  Google Scholar 

  41. Efstathiou JA, Bae K, Shipley WU, Hanks GE, Pilepich MV, Sandler HM, et al. Cardiovascular mortality and duration of androgen deprivation for locally advanced prostate cancer: analysis of RTOG 92-02. Eur Urol. 2008;54:816–23.

    CAS  PubMed  Google Scholar 

  42. Roach M 3rd, Bae K, Speight J, Wolkov HB, Rubin P, Lee RJ, et al. Short-term neoadjuvant androgen deprivation therapy and external-beam radiotherapy for locally advanced prostate cancer: long-term results of RTOG 8610. J Clin Oncol. 2008;26:585–91.

    PubMed  Google Scholar 

  43. D’Amico AV, Denham JW, Crook J, Chen MH, Goldhaber SZ, Lamb DS, et al. Influence of androgen suppression therapy for prostate cancer on the frequency and timing of fatal myocardial infarctions. J Clin Oncol. 2007;25:2420–5.

    PubMed  Google Scholar 

  44. Tsai HK, D'Amico AV, Sadetsky N, Chen MH, Carroll PR. Androgen deprivation therapy for localized prostate cancer and the risk of cardiovascular mortality. J Natl Cancer Inst. 2007;99:1516–24.

    PubMed  Google Scholar 

  45. Nanda A, Chen MH, Braccioforte MH, Moran BJ, D'Amico AV. Hormonal therapy use for prostate cancer and mortality in men with coronary artery disease-induced congestive heart failure or myocardial infarction. Jama. 2009;302:866–73.

    CAS  PubMed  Google Scholar 

  46. Albertsen PC, Klotz L, Tombal B, Grady J, Olesen TK, Nilsson J. Cardiovascular morbidity associated with gonadotropin releasing hormone agonists and an antagonist. Eur Urol. 2014;65:565–73.

    CAS  PubMed  Google Scholar 

  47. Perrone V, Degli Esposti L, Giacomini E, Veronesi C, Blini V, Oderda M. Cardiovascular risk profile in prostate cancer patients treated with GnRH agonists versus antagonists: an Italian real-world analysis. Ther Clin Risk Manag. 2020;16:393–401.

    CAS  PubMed  PubMed Central  Google Scholar 

  48. Margel D, Peer A, Ber Y, Shavit-Grievink L, Tabachnik T, Sela S, et al. Cardiovascular morbidity in a randomized trial comparing GnRH agonist and GnRH antagonist among patients with advanced prostate cancer and preexisting cardiovascular disease. J Urol. 2019;202:1199–208.

    PubMed  Google Scholar 

  49. Higano CS. Cardiovascular disease and androgen axis–targeted drugs for prostate cancer. N Engl J Med. 2020;382:2257–9.

    CAS  PubMed  Google Scholar 

  50. Tayek JA, Heber D, Byerley LO, Steiner B, Rajfer J, Swerdloff RS. Nutritional and metabolic effects of gonadotropin-releasing hormone agonist treatment for prostate cancer. Metabolism. 1990;39:1314–9.

    CAS  PubMed  Google Scholar 

  51. Berruti A, Dogliotti L, Terrone C, Cerutti S, Isaia G, Tarabuzzi R, et al. Changes in bone mineral density, lean body mass and fat content as measured by dual energy x-ray absorptiometry in patients with prostate cancer without apparent bone metastases given androgen deprivation therapy. J Urol. 2002;167:2361–7 discussion 2367.

    PubMed  Google Scholar 

  52. Smith MR. Changes in fat and lean body mass during androgen-deprivation therapy for prostate cancer. Urology. 2004;63:742–5.

    PubMed  Google Scholar 

  53. Lee H, McGovern K, Finkelstein JS, Smith MR. Changes in bone mineral density and body composition during initial and long-term gonadotropin-releasing hormone agonist treatment for prostate carcinoma. Cancer. 2005;104:1633–7.

    CAS  PubMed  Google Scholar 

  54. Smith MR, Finkelstein JS, McGovern FJ, Zietman AL, Fallon MA, Schoenfeld DA, et al. Changes in body composition during androgen deprivation therapy for prostate cancer. J Clin Endocrinol Metab. 2002;87:599–603.

    CAS  PubMed  Google Scholar 

  55. Dockery F, Bulpitt CJ, Agarwal S, Donaldson M, Rajkumar C. Testosterone suppression in men with prostate cancer leads to an increase in arterial stiffness and hyperinsulinaemia. Clin Sci (Lond). 2003;104:195–201.

    CAS  Google Scholar 

  56. Smith MR, Lee H, Nathan DM. Insulin sensitivity during combined androgen blockade for prostate cancer. J Clin Endocrinol Metab. 2006;91:1305–8.

    CAS  PubMed  Google Scholar 

  57. Braga-Basaria M, Dobs AS, Muller DC, Carducci MA, John M, Egan J, et al. Metabolic syndrome in men with prostate cancer undergoing long-term androgen-deprivation therapy. J Clin Oncol. 2006;24:3979–83.

    PubMed  Google Scholar 

  58. Langer C, Gansz B, Goepfert C, Engel T, Uehara Y, von Dehn G, et al. Testosterone up-regulates scavenger receptor BI and stimulates cholesterol efflux from macrophages. Biochem Biophys Res Commun. 2002;296:1051–7.

    CAS  PubMed  Google Scholar 

  59. Qiu Y, Yanase T, Hu H, Tanaka T, Nishi Y, Liu M, et al. Dihydrotestosterone suppresses foam cell formation and attenuates atherosclerosis development. Endocrinology. 2010;151:3307–16.

    CAS  PubMed  Google Scholar 

  60. Nettleship JE, Jones TH, Channer KS, Jones RD. Physiological testosterone replacement therapy attenuates fatty streak formation and improves high-density lipoprotein cholesterol in the Tfm mouse: an effect that is independent of the classic androgen receptor. Circulation. 2007;116:2427–34.

    CAS  PubMed  Google Scholar 

  61. Sung N, Salazar García MD, Dambaeva S, Beaman KD, Gilman-Sachs A, Kwak-Kim J. Gonadotropin-releasing hormone analogues lead to pro-inflammatory changes in T lymphocytes. Am J Reprod Immunol. 2016;76:50–8.

    CAS  PubMed  Google Scholar 

  62. Corcoran MP, Meydani M, Lichtenstein AH, Schaefer EJ, Dillard A, Lamon-Fava S. Sex hormone modulation of proinflammatory cytokine and C-reactive protein expression in macrophages from older men and postmenopausal women. J Endocrinol. 2010;206:217–24.

    CAS  PubMed  PubMed Central  Google Scholar 

  63. Hatakeyama H, Nishizawa M, Nakagawa A, Nakano S, Kigoshi T, Uchida K. Testosterone inhibits tumor necrosis factor-alpha-induced vascular cell adhesion molecule-1 expression in human aortic endothelial cells. FEBS Lett. 2002;530:129–32.

    CAS  PubMed  Google Scholar 

  64. Smith JC, Bennett S, Evans LM, Kynaston HG, Parmar M, Mason MD, et al. The effects of induced hypogonadism on arterial stiffness, body composition, and metabolic parameters in males with prostate cancer. J Clin Endocrinol Metab. 2001;86:4261–7.

    CAS  PubMed  Google Scholar 

  65. Dockery F, Bulpitt CJ, Agarwal S, Vernon C, Rajkumar C. Effect of androgen suppression compared with androgen receptor blockade on arterial stiffness in men with prostate cancer. J Androl. 2009;30:410–5.

    CAS  PubMed  Google Scholar 

  66. Iacovelli R, Verri E, Cossu Rocca M, Aurilio G, Cullurà D, De Cobelli O, et al. The incidence and relative risk of cardiovascular toxicity in patients treated with new hormonal agents for castration-resistant prostate cancer. Eur J Cancer. 2015;51:1970–7.

    CAS  PubMed  Google Scholar 

  67. Bretagne M, Lebrun-Vignes B, Pariente A, Shaffer CM, Malouf GG, Dureau P, et al. Heart failure and atrial tachyarrhythmia on abiraterone: a pharmacovigilance study. Arch Cardiovasc Dis. 2020;113:9–21.

    PubMed  Google Scholar 

  68. Tsao PA, Estes JP, Griggs JJ, Smith DC, Caram MEV. Cardiovascular and metabolic toxicity of abiraterone in castration-resistant prostate cancer: post-marketing experience. Clin Genitourin Cancer. 2019;17:e592–601.

    PubMed  Google Scholar 

  69. Fizazi K, Scher HI, Molina A, Logothetis CJ, Chi KN, Jones RJ, et al. Abiraterone acetate for treatment of metastatic castration-resistant prostate cancer: final overall survival analysis of the COU-AA-301 randomised, double-blind, placebo-controlled phase 3 study. Lancet Oncol. 2012;13:983–92.

    CAS  PubMed  Google Scholar 

  70. Ridley JM, Shuba YM, James AF, Hancox JC. Modulation by testosterone of an endogenous hERG potassium channel current. J Physiol Pharmacol. 2008;59:395–407.

    CAS  PubMed  Google Scholar 

  71. Kakar SS, Jennes L. Expression of gonadotropin-releasing hormone and gonadotropin-releasing hormone receptor mRNAs in various non-reproductive human tissues. Cancer Lett. 1995;98:57–62.

    CAS  PubMed  Google Scholar 

  72. Dong F, Skinner DC, Wu TJ, Ren J. The heart: a novel gonadotrophin-releasing hormone target. J Neuroendocrinol. 2011;23:456–63.

    CAS  PubMed  Google Scholar 

  73. Tannock IF, de Wit R, Berry WR, Horti J, Pluzanska A, Chi KN, et al. Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. N Engl J Med. 2004;351:1502–12.

    CAS  PubMed  Google Scholar 

  74. Sweeney CJ, Chen YH, Carducci M, Liu G, Jarrard DF, Eisenberger M, et al. Chemohormonal therapy in metastatic hormone-sensitive prostate cancer. N Engl J Med. 2015;373:737–46.

    CAS  PubMed  PubMed Central  Google Scholar 

  75. Vale CL, Burdett S, Rydzewska LHM, Albiges L, Clarke NW, Fisher D, et al. Addition of docetaxel or bisphosphonates to standard of care in men with localised or metastatic, hormone-sensitive prostate cancer: a systematic review and meta-analyses of aggregate data. Lancet Oncol. 2016;17:243–56.

    CAS  PubMed  PubMed Central  Google Scholar 

  76. Rowinsky EK, Eisenhauer EA, Chaudhry V, Arbuck SG, Donehower RC. Clinical toxicities encountered with paclitaxel (Taxol). Semin Oncol. 1993;20:1–15.

    CAS  PubMed  Google Scholar 

  77. Biganzoli L, Cufer T, Bruning P, Coleman RE, Duchateau L, Rapoport B, et al. Doxorubicin-paclitaxel: a safe regimen in terms of cardiac toxicity in metastatic breast carcinoma patients. Results from a European Organization for Research and Treatment of Cancer multicenter trial. Cancer. 2003;97:40–5.

    CAS  PubMed  Google Scholar 

  78. Giordano SH, Booser DJ, Murray JL, Ibrahim NK, Rahman ZU, Valero V, et al. A detailed evaluation of cardiac toxicity: a phase II study of doxorubicin and one- or three-hour-infusion paclitaxel in patients with metastatic breast cancer. Clin Cancer Res. 2002;8:3360–8.

    CAS  PubMed  Google Scholar 

  79. Rahman Z, Champlin R, Rondon G, Frye D, Valero V, Mehra R, et al. Phase I/II study of dose-intense doxorubicin/paclitaxel/cyclophosphamide with peripheral blood progenitor cells and cytokine support in patients with metastatic breast cancer. Semin Oncol. 1997;24:S17-77–s17-80.

    Google Scholar 

  80. Lenneman CG, Sawyer DB. Cardio-oncology: an update on cardiotoxicity of cancer-related treatment. Circ Res. 2016;118:1008–20.

    CAS  PubMed  Google Scholar 

  81. de Bono J, Mateo J, Fizazi K, Saad F, Shore N, Sandhu S, et al. Olaparib for metastatic castration-resistant prostate cancer. N Engl J Med. 2020;382:2091–102.

    PubMed  Google Scholar 

  82. Henning RJ, Bourgeois M, Harbison RD. Poly(ADP-ribose) polymerase (PARP) and PARP inhibitors: mechanisms of action and role in cardiovascular disorders. Cardiovasc Toxicol. 2018;18:493–506.

    CAS  PubMed  Google Scholar 

  83. Sarszegi Z, Bognar E, Gaszner B, Kónyi A, Gallyas F, Sumegi B, et al. BGP-15, a PARP-inhibitor, prevents imatinib-induced cardiotoxicity by activating Akt and suppressing JNK and p38 MAP kinases. Mol Cell Biochem. 2012;365:129–37.

    CAS  PubMed  Google Scholar 

  84. Ali M, Kamjoo M, Thomas HD, Kyle S, Pavlovska I, Babur M, et al. The clinically active PARP inhibitor AG014699 ameliorates cardiotoxicity but does not enhance the efficacy of doxorubicin, despite improving tumor perfusion and radiation response in mice. Mol Cancer Ther. 2011;10:2320–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  85. Center for Drug Evaluation and Research. Multidisciplinary Review and Evaluation: Rubraca (rucaparib). Food and Drug Administration (FDA); 2016 . https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/209115Orig1s000MultiDisciplineR.pdf (26 June 2020).

  86. Segan L, Beekman A, Parfrey S, Perrin M. PARP inhibitor-induced torsades de pointes in long QT syndrome: a case report. Eur Heart J Case Rep. 2019;4(1):1–5.

  87. Lyon AR, Yousaf N, Battisti NML, Moslehi J, Larkin J. Immune checkpoint inhibitors and cardiovascular toxicity. Lancet Oncol. 2018;19:e447–58.

    CAS  PubMed  Google Scholar 

  88. Flynn MJ, Larkin JMG. Novel combination strategies for enhancing efficacy of immune checkpoint inhibitors in the treatment of metastatic solid malignancies. Expert Opin Pharmacother. 2017;18:1477–90.

    CAS  PubMed  Google Scholar 

  89. Kantoff PW, Higano CS, Shore ND, Berger ER, Small EJ, Penson DF, et al. Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N Engl J Med. 2010;363:411–22.

    CAS  PubMed  Google Scholar 

  90. Sharma P, Pachynski RK, Narayan V, Flechon A, Gravis G, Galsky MD, et al. Initial results from a phase II study of nivolumab (NIVO) plus ipilimumab (IPI) for the treatment of metastatic castration-resistant prostate cancer (mCRPC; CheckMate 650). J Clin Oncol. 2019;37(suppl 7S):abstr 142.

    Google Scholar 

  91. Antonarakis ES, Piulats JM, Gross-Goupil M, Goh J, Ojamaa K, Hoimes CJ, et al. Pembrolizumab for treatment-refractory metastatic castration-resistant prostate cancer: multicohort, open-label phase II KEYNOTE-199 study. J Clin Oncol. 2020;38:395–405.

    CAS  PubMed  Google Scholar 

  92. Moslehi JJ, Salem JE, Sosman JA, Lebrun-Vignes B, Johnson DB. Increased reporting of fatal immune checkpoint inhibitor-associated myocarditis. Lancet. 2018;391:933.

    PubMed  PubMed Central  Google Scholar 

  93. Zhang L, Jones-O'Connor M, Awadalla M, Zlotoff DA, Thavendiranathan P, Groarke JD, et al. Cardiotoxicity of immune checkpoint inhibitors. Curr Treat Options Cardiovasc Med. 2019;21:32.

    PubMed  Google Scholar 

  94. Zhang L, Zlotoff DA, Awadalla M, Mahmood SS, Nohria A, MZO H, et al. Major adverse cardiovascular events and the timing and dose of corticosteroids in immune checkpoint inhibitor-associated myocarditis. Circulation. 2020;141:2031–4.

    CAS  PubMed  PubMed Central  Google Scholar 

  95. Bhatia N, Santos M, Jones LW, Beckman JA, Penson DF, Morgans AK, et al. Cardiovascular effects of androgen deprivation therapy for the treatment of prostate cancer: ABCDE steps to reduce cardiovascular disease in patients with prostate cancer. Circulation. 2016;133:537–41.

    PubMed  PubMed Central  Google Scholar 

  96. Barber M, Nguyen LS, Wassermann J, Spano JP, Funck-Brentano C, Salem JE. Cardiac arrhythmia considerations of hormone cancer therapies. Cardiovasc Res. 2019;115:878–94.

    CAS  PubMed  Google Scholar 

  97. Tsugu T, Nagatomo Y, Nakajima Y, Kageyama T, Akise Y, Endo J, et al. Cancer therapeutics-related cardiac dysfunction in a patient treated with abiraterone for castration-resistant prostate cancer. J Med Ultrason (2001). 2019;46:239–43.

    Google Scholar 

  98. Armenian SH, Lacchetti C, Barac A, Carver J, Constine LS, Denduluri N, et al. Prevention and monitoring of cardiac dysfunction in survivors of adult cancers: American Society of Clinical Oncology Clinical Practice Guideline. J Clin Oncol. 2017;35:893–911.

    PubMed  Google Scholar 

  99. Darby SC, Ewertz M, McGale P, Bennet AM, Blom-Goldman U, Bronnum D, et al. Risk of ischemic heart disease in women after radiotherapy for breast cancer. N Engl J Med. 2013;368:987–98.

    CAS  PubMed  Google Scholar 

  100. van Nimwegen FA, Schaapveld M, Cutter DJ, Janus CP, Krol AD, Hauptmann M, et al. Radiation dose-response relationship for risk of coronary heart disease in survivors of Hodgkin lymphoma. J Clin Oncol. 2016;34:235–43.

    PubMed  Google Scholar 

  101. Demissei BG, Freedman G, Feigenberg SJ, Plastaras JP, Maity A, Smith AM, et al. Early changes in cardiovascular biomarkers with contemporary thoracic radiation therapy for breast cancer, lung cancer, and lymphoma. Int J Radiat Oncol Biol Phys. 2019;103:851–60.

    CAS  PubMed  Google Scholar 

  102. Demissei BG, Hubbard RA, Zhang L, Smith AM, Sheline K, McDonald C, et al. Changes in cardiovascular biomarkers with breast cancer therapy and associations with cardiac dysfunction. J Am Heart Assoc. 2020;9:e014708.

    CAS  PubMed  PubMed Central  Google Scholar 

  103. Dockery F, Bulpitt CJ, Agarwal S, Vernon C, Nihoyannopoulos P, Kemp M, et al. Anti-androgens increase N-terminal pro-BNP levels in men with prostate cancer. Clin Endocrinol. 2008;68:59–65.

    CAS  Google Scholar 

  104. Anand SS, Eikelboom JW, Dyal L, Bosch J, Neumann C, Widimsky P, et al. Rivaroxaban plus aspirin versus aspirin in relation to vascular risk in the COMPASS trial. J Am Coll Cardiol. 2019;73:3271–80.

    CAS  PubMed  Google Scholar 

  105. Melloni C, Slovin SF, Blemings A, Goodman SG, Evans CP, Nilsson J, et al. Cardiovascular safety of degarelix versus leuprolide for advanced prostate cancer. JACC Cardio Oncol. 2020;2:70.

    Google Scholar 

Download references

Author information

Author notes

  1. Avirup Guha and Arjun K. Ghosh contributed equally to this work.

Authors and Affiliations

  1. Division of Cardiovascular Medicine, Department of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, OH, USA

    Courtney M. Campbell MD, PhD

  2. Division of Cardiology, Cardio-Oncology Center of Excellence, Washington University in St. Louis School of Medicine, St. Louis, MO, USA

    Kathleen W. Zhang MD

  3. Diabetes Day Centre, University Hospital, Ayr, UK

    Andrew Collier MD, FRCPE

  4. Department of Oncology, University College London Cancer Institute, London, UK

    Mark Linch PhD, FRCP

  5. Department of Urology, University Hospitals Cleveland Medical Center, Case Western Reserve University School of Medicine, Cleveland, OH, USA

    Adam C. Calaway MD & Lee Ponsky MD

  6. Harrington Heart and Vascular Institute, Case Western Reserve University, Cleveland, OH, USA

    Avirup Guha MD

  7. Cardio-Oncology Service, Barts Heart Centre, St. Bartholomew’s Hospital West Smithfield, London, UK

    Arjun K. Ghosh MBBS, PhD, FRCP

  8. Cardio-Oncology Service, Hatter Cardiovascular Institute, University College London Hospital, London, UK

    Arjun K. Ghosh MBBS, PhD, FRCP

Authors
  1. Courtney M. Campbell MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kathleen W. Zhang MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Andrew Collier MD, FRCPE
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Mark Linch PhD, FRCP
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Adam C. Calaway MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Lee Ponsky MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Avirup Guha MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Arjun K. Ghosh MBBS, PhD, FRCP
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Arjun K. Ghosh MBBS, PhD, FRCP.

Ethics declarations

Conflict of Interest

Courtney M. Campbell declares that she has no conflict of interest. Kathleen W. Zhang declares that she has no conflict of interest. Andrew Collier declares that he has no conflict of interest. Mark Linch declares that he has no conflict of interest. Adam Christopher Calaway declares that he has no conflict of interest. Lee Ponsky declares that he has no conflict of interest. Avirup Guha declares that he has no conflict of interest. Arjun K. Ghosh declares that he has no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This article is part of the Topical Collection on Cardio-oncology

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Campbell, C.M., Zhang, K.W., Collier, A. et al. Cardiovascular Complications of Prostate Cancer Therapy. Curr Treat Options Cardio Med 22, 69 (2020). https://doi.org/10.1007/s11936-020-00873-3

Download citation

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s11936-020-00873-3

Keywords

Search

Navigation