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Supportive Care in Cancer

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01-09-2019 | Prostate Cancer | Review Article

Management of anticoagulation in patients with metastatic castration–resistant prostate cancer receiving abiraterone + prednisone

Authors: Samuel Dubinsky, Alia Thawer, Anne G. McLeod, Thomas R.J. McFarlane, Urban Emmenegger

Published in: Supportive Care in Cancer | Issue 9/2019

Abstract

Purpose

Abiraterone has been proven to be an effective agent used in the management of metastatic castration–resistant prostate cancer, significantly improving overall and progression-free survival. Due to the pharmacodynamic and pharmacokinetic properties of abiraterone, concurrent use with anticoagulation may pose a challenge for clinicians. Thrombosis within the cancer setting continues to increase patient mortality; therefore, appropriate anticoagulation through the use of a management algorithm can reduce adverse events and increase quality of life.

Methods

A review of the literature was preformed by a medical oncologist, haematologist and pharmacists to identify relevant randomized controlled trials, meta-analyses and retrospective studies. Major society guidelines were reviewed to further aid in developing the anticoagulation protocol for non-valvular atrial fibrillation and venous thromboembolism within this patient population. After reviewing the literature, a clinical framework was designed to aid clinicians in the management of those patients receiving abiraterone concurrently with an anticoagulant.

Results

In this review, we describe the potential interactions between abiraterone and various anticoagulants and provide management strategies based on the most recent literature for atrial fibrillation, venous thromboembolism and mechanical heart valves to avoid potential drug–drug interactions.

Conclusion

Abiraterone therapy has become a mainstay of the management of advanced prostate cancer and is often used over prolonged years. In this review, we have summarized a framework of how to use abiraterone in men with prostate cancer on anticoagulants. Evidence available to date suggests that patients with an indication for anticoagulation such as atrial fibrillation, venous thromboembolism and mechanical heart valves can be treated safely with abiraterone in the appropriate setting, with appropriate monitoring.

Cooperberg MR, Chan JM (2017) Epidemiology of prostate cancer. World J Urol 35(6):849. https://doi.org/10.1007/s00345-017-2038-0 CrossRefPubMed

Torre LA, Bray F, Siegal RL et al (2015) Global cancer statistics, 2012. CA Cancer J Clin 65:87–108. https://doi.org/10.3322/caac.21262 CrossRefPubMed

Stein PD, Hull RD, Kayali F et al (2004) Venous thromboembolism according to age: the impact of an aging population. Arch Intern Med 164(20):2260–2265CrossRefPubMed

Marinigh R, Lip GYH, Fiotti N, Giansanate C, Lane DA (2010) Age as a risk factor for stroke in atrial fibrillation patients: implications for thromboprophylaxis. JACC 56(11). https://doi.org/10.1016/j.jacc.2010.05.028

Khorana AA, Connolly GC (2009) Assessing risk of venous thromboembolism in the patient with cancer. J Clin Oncol 27:4839–4847. https://doi.org/10.1200/JCO.2009.22.3271 CrossRefPubMedPubMedCentral

Weiner AB, Matulewicz RS, Eggener SE, Schaeffer EM (2016) Increasing incidence of metastatic prostate cancer in the United States (2004-2013). Prostate Cancer Prostatic Dis 19:395–397. https://doi.org/10.1038/pcan.2016.30 CrossRefPubMed

Lane DA, Skjoth F, Lip GYH, Larsen TB, Kotecha D (2017) Temporal trends in incidence, prevalence, and mortality of atrial fibrillation in primary care. JAHA 6(5). https://doi.org/10.1161/JAHA.116.00515

Easaw JC, Shea-Budgell MA, Wu CMJ et al (2015) Canadian consensus recommendations on the management of venous thromboembolism in patients with cancer. Part 1: prophylaxis. Curr Oncol 22(2):133–143. https://doi.org/10.3747/co.22.2586 CrossRefPubMedPubMedCentral

Horsted F, West J, Grainge MJ (2012) Risk of venous thromboembolism in patients with cancer: a systematic review and meta-analysis. PLoS Med 9:e1001275. https://doi.org/10.1371/journal.pmed.1001275 CrossRefPubMedPubMedCentral

10.

Rehman Y, Rosenberg JE (2012) Abiraterone acetate: oral androgen biosynthesis inhibitor for treatment of castration-resistant prostate cancer. Drug Des Devel Ther 6:13–18. https://doi.org/10.2147/DDDT.S15850 CrossRefPubMedPubMedCentral

11.

Agarwal N, Hutson TE, Sonpavde G, Vogelzang (2010) Abiraterone acetate: a promising drug for the treatment of castration-resistant prostate cancer. Future Oncol 6(5):665–679. https://doi.org/10.2217/fon.10.48 CrossRefPubMed

12.

Bruno RD, Njar VCO, Vasaitis TS (2011) CYP17 inhibitors for prostate cancer therapy. J Steroid Biochem Mol Biol 125(1–2):23–31. https://doi.org/10.1016/j.jsbmb.2010.11.005 CrossRefPubMed

13.

Ryan CJ, Smith MR, de Bono J et al (2013) Abiraterone in metastatic prostate cancer without previous chemotherapy. N Engl J Med 368:138–148. https://doi.org/10.1056/NEJMoa1209096 CrossRefPubMed

14.

James ND, de Bono JS, Spears MR et al (2017) Abiraterone for prostate cancer not previously treated with hormone therapy. N Engl J Med 377:388–351. https://doi.org/10.1056/NEJMoa1702900 CrossRef

15.

Fizazi K, Tran NP, Fein L et al (2017) Abiraterone plus prednisone in metastatic, castration-sensitive prostate cancer. N Engl J Med 377:352–360. https://doi.org/10.1056/NEJMoa1704174 CrossRefPubMed

16.

Han CS, Kim IY, Patel R (2015) Pharmacokinetics, pharmacodynamics and clinical efficacy of abiraterone acetate for treating metastatic castration-resistant prostate cancer. Expert Opin Drug Metab Toxicol 11(6):967–975. https://doi.org/10.1517/17425255.2015.1041918 CrossRefPubMed

17.

Benoist GE, Hendriks RJ, Mulders PFA et al (2016) Pharmacokinetic aspect of the two novel oral drugs used for metastatic castration-resistant prostate cancer: abiraterone acetate and enzalutamide. Clin Pharmacokinet 55(11):1369–1380. https://doi.org/10.1007/s40262-016-0403-6 CrossRefPubMedPubMedCentral

18.

Pia A, Vignani F, Attard G et al (2013) Strategies for managing ACTH dependent mineralocorticoid excess induced by abiraterone. Cancer Treat Rev 39(8):966–973. https://doi.org/10.1016/j.ctrv.2013.03.003. ReviewCrossRefPubMed

19.

Narum S, Westergren T, Klemp M (2014) Corticosteroids and risk of gastrointestinal bleeding: a systematic review and meta-analysis. BMJ Open 4(5). https://doi.org/10.1136/bmjopen-2013-004587

20.

Lanza FL, Chan FKL, Quigley EMM et al (2009) Prevention of NSAID-related ulcer complications. Am J Gastroenterol 104:728–738. https://doi.org/10.1038/ajg.2009.115 CrossRefPubMed

21.

Khorana AA, Francis CW, Culakova E, Kuderer NM, Lyman GH (2007) Thromboembolism is a leading cause of death in cancer patients receiving outpatient chemotherapy. J Thromb Haemost 5:632–634CrossRefPubMed

22.

Macle L, Cairns J, Leblanc L et al (2016) 2016 focused update of the Canadian cardiovascular society guidelines for the management of atrial fibrillation. CJC 32(10):1170–1185. https://doi.org/10.1016/j.cjca.2016.07.591 CrossRef

23.

Patel R, Gutierrez A, Rybicki L, Khorana AA (2017) Usefulness of CHADS2 and CHA2DS2-VASc scores for stroke prediction in patients with cancer and atrial fibrillation. Am J Cardiol 120(12):2182–2186CrossRef

24.

Yeh CH, Gross PL, Weitz JI (2014) Evolving use of new oral anticoagulants for treatment of venous thromboembolism. Blood. 124(7):1020–1028CrossRefPubMedPubMedCentral

25.

Dickmann B, Ahlbrecht J, Ay C, Dunkler D, Thaler J, Scheithauer W, Quehenberger P, Zielinski C, Pabinger I (2013) Regional lymph node metastases are a strong risk factor for venous thromboembolism: results from the Vienna Cancer and Thrombosis Study. Haematologica. 98:1309–1314. https://doi.org/10.3324/haematol.2012.073338 CrossRefPubMedPubMedCentral

26.

Van Hemelrijck MV, Adolfsson J, Garmo H et al (2010) Risk of thromboembolic disease in men with prostate cancer: results from the population-based PCBaSe Sweden. Lancet Oncol 11(5):450–458. https://doi.org/10.1016/S1470-2045(10)70038-3 CrossRefPubMedPubMedCentral

27.

Jamani R, Lee EK, Berry SR et al (2016) High prevalence of potential drug-drug interactions in patients with castration-resistant prostate cancer treated with abiraterone acetate. Eur J Clin Pharmacol 72(11):1391–1399CrossRefPubMed

28.

Elyamany G, Alzahrani AM, Bukary E (2014) Cancer-associated thrombosis: an overview. Clin Med Insights Oncol 8:129–137CrossRefPubMedPubMedCentral

29.

Kearon C, Akl EA, Comerota AJ et al (2012) Antithrombotic therapy for VTE. CHEST. 141(2):419–494CrossRef

30.

Eikelboom J, Merli G (2016) Bleeding with direct oral anticoagulants vs. warfarin: clinical experience. Am J Med 129(11):33–40. https://doi.org/10.1016/j.amjmed.2016.06.003 CrossRef

31.

Fitzgerald JL, Howes LG (2016) Drug interactions of direct acting oral anticoagulants. Drug Saf 39(9):841–845. https://doi.org/10.1007/s40264-016-0443-8 CrossRefPubMed

32.

Di Minno A, Frigerio B, Spadarella G. et. al. Old and new oral anticoagulants: food, herbal medicines and drug interactions. Blood Rev 2017; 31(4): 193–203

33.

Burnett A, Siegal D, Crowther M (2017) Specific antidotes for bleeding associated with direct oral anticoagulants. BMJ 357:j2216. https://doi.org/10.1136/bmj.j2216 CrossRefPubMed

34.

Nutescu EA, Burnett A, Fanikos J, Spinler S, Wittkowsky A (2016) Pharmacology of anticoagulants used in the treatment of venous thromboembolism. J Thromb Thrombolysis 41:15–31. https://doi.org/10.1007/s11239-015-1314-3 CrossRefPubMedPubMedCentral

35.

Patel MR, Mahaffey KW, Jyotsna G (2011) Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med 365:883–891. https://doi.org/10.1056/NEJMoa1009638 CrossRefPubMed

36.

EINSTEIN Investigators (2010) Oral rivaroxaban for symptomatic venous thromboembolism. N Engl J Med 363:2499–2510. https://doi.org/10.1056/NEJMoa1007903 CrossRef

37.

EINSTEIN-PE Investigators (2012) Oral rivaroxaban for the treatment of symptomatic pulmonary embolism. N Engl J Med 366:1287–1297. https://doi.org/10.1056/NEJMoa1113572 CrossRef

38.

Young A, Marshall A, Thirlwall J et al (2018) Comparison of an oral factor Xa inhibitor with low molecular weight heparin in patients with cancer with venous thromboembolism: results of a randomized trial (SELECT-D). J Clin Oncol:JCO2018788034. https://doi.org/10.1200/JCO.2018.78.8034

39.

Bayer INC (2018) Xarelto product monograph. Bayer INC., Mississauga

40.

Giugliano RP, Ruff CT, Braunwald E et al (2013) Edoxaban versus warfarin in patients with atrial fibrillation. N Engl J Med 269:2093–2104. https://doi.org/10.1056/NEJMoa1310907 CrossRef

41.

Servier Pharmaceuticals (2016) Lixiana product monograph. Servier Canada INC., Laval

42.

Hokusai-VTE Investigators (2013) Edoxaban versus warfarin for the treatment of symptomatic venous thromboembolism. N Engl J Med 369:1406–1415. https://doi.org/10.1056/NEJMoa1306638 CrossRef

43.

Raskob GE, van Es N, Verhamme P et al (2018) Edoxaban for the treatment of cancer-associated venous thromboembolism. N Engl J Med 378:615–624. https://doi.org/10.1056/NEJMoa1711948 CrossRefPubMed

44.

Parasrampuria DA, Truitt KE (2016) Pharmacokinetics and pharmacodynamics of edoxaban, a non-vitamin K antagonist oral anticoagulant that inhibits clotting factor Xa. Clin Pharmacokinet 55:641–655. https://doi.org/10.1007/s40262-015-0342-7 CrossRefPubMed

45.

Granger CB, Alexander JH, McMurray JJV et al (2011) Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med 365:981–992. https://doi.org/10.1056/NEJMoa1107039 CrossRefPubMed

46.

Agnelli G, Buller HR, Cohen A et al (2013) Oral apixaban for the treatment of acute venous thromboembolism. N Engl J Med 369:799–808. https://doi.org/10.1056/NEJMoa1302507 CrossRefPubMed

47.

Agnelli G, Buller HR, Cohen A et al (2015) Oral apixaban for the treatment of venous thromboembolism in cancer patients: results from the AMPLIFY trial. J Thromb Haemost 13:2187–2191CrossRefPubMed

48.

Lyman GH, Bohlke K, Khorana AA et al (2015) Venous thromboembolism prophylaxis and treatment in patients with cancer: American society of clinical oncology clinical practice guideline update 2014. J Clin Oncol 33(6):654–656CrossRefPubMedPubMedCentral

49.

Wagman LD, Baird MF, Bennett CL et al (2006) Venous thromboembolic disease: clinical practice guidelines in oncology. J Natl Compr Cancer Netw 4:838–869CrossRef

50.

Pfizer Pharmaceuticals (2016) Eliquis product monograph. Pfizer Canada INC., Kirkland

51.

Connolly SJ, Ezekowitz MD, Yusuf S et al (2009) Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med 361:1139–1151. https://doi.org/10.1056/NEJMoa0905561 CrossRefPubMed

52.

Schulman S, Kearon C, Kakkar AK et al (2009) Dabigatran versus warfarin in the treatment of acute venous thromboembolism. N Engl J Med 361:2342–2352. https://doi.org/10.1056/NEJMoa0906598 CrossRefPubMed

53.

Holster IL, Valkhoff VE, Kuipers EJ, Tjwa ETTL (2013) New oral anticoagulants increase risk for gastrointestinal bleeding: a systematic review and meta-analysis. Gastroenterology 145(1):105–112. https://doi.org/10.1053/j.gastro.2013.02.041 CrossRefPubMed

54.

Abraham NS, Singh S, Alexander GC et al (2015) Comparative risk of gastrointestinal bleeding with dabigatran, rivaroxaban, and warfarin: population based cohort study. BMJ 350:1857. https://doi.org/10.1136/bmj.h1857 CrossRef

55.

Boehringer Ingelhem Pharmaceuticals (2016) Pradaxa product monograph. Boehringer Ingelheim Canada Ltd, Burlington

56.

Lee AYY, Levine MN, Baker RI et al (2003) Low-molecular-weight heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer. N Engl J Med 349:146–153. https://doi.org/10.1056/NEJMoa025313 CrossRefPubMed

57.

Vedovati MC, Germini F, Agnelli G, Becattini C (2015) Direct oral anticoagulants in patients with VTE and cancer. CHEST. 147(2):475–483CrossRefPubMed

58.

Sobieraj DM, Baker WL, Smith E et al (2018) Anticoagulation for the treatment of cancer-associated thrombosis: a systematic review and network meta-analysis of randomized trials. Clin Appl Thromb Hemost 24(9S):182S–187S. https://doi.org/10.1177/1076029618800792 CrossRefPubMedPubMedCentral

59.

Camm AJ (2001) Atrial fibrillation: is there a role for low-molecular-weight heparin? Clin Cariol 24(3):115–119

60.

Sands CD, Chan ES, Welty TE (2002) Revisiting the significance of warfarin protein-binding displacement interactions. Ann Pharmacother 36:1642–1644CrossRefPubMed

61.

Schmidt S, Gonzalez D, Derendorf H (2010) Significance of protein binding in pharmacokinetics and pharmacodynamics. J Pharm Sci 99(3):1107–1112. https://doi.org/10.1002/jps.21916 CrossRefPubMed

62.

Juurlink DN (2007) Drug interactions with warfarin: what clinicians need to know. CMAJ. 177(4):369–371CrossRefPubMedPubMedCentral

63.

Holbrook A, Schulman S, Guyatt GH et al (2012) Evidence-based management of anticoagulant therapy. CHEST. 141(2):152–184CrossRef

64.

Nishimura RA, Otto CM, Bonow RO et al (2017) 2017 AHA/ACC focused update of the 2014 AHA/ACC guideline for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association task force on clinical practice guidelines. JACC. 70(2):252–289CrossRefPubMed

65.

Whitlock RP, Sun JC, Fremes SE, Rubens FD, Teoh KH Antithrombotic and thrombolytic therapy for valvular disease: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest physicians evidence-based clinical practice guidelines. CHEST 141(2):576–600. https://doi.org/10.1378/chest.11-2305

66.

Van de Werf F, Brueckmann M, Connolly SJ et al (2012) A comparison of dabigatran etexilate with warfarin in patients with mechanical heart valves: the randomized phase II study to evaluate the safety and pharmacokinetics of oral dabigatran etexilate in patients after heart valve replacement (RE-ALIGN). AHJ. 163(6):931–937CrossRefPubMed

67.

Goldberg T, Berrios-Colon E (2013) Abiraterone (Zytiga), a novel agent for the management of castration-resistant prostate cancer. PT. 38(1):23–26

68.

Carrier M, Blais N, Crowther M et al (2018) Treatment algorithm in cancer-associated thrombosis: Canadian expert consensus. Curr Oncol 5:329–337

Title: Management of anticoagulation in patients with metastatic castration–resistant prostate cancer receiving abiraterone + prednisone
Authors: Samuel Dubinsky
Alia Thawer
Anne G. McLeod
Thomas R.J. McFarlane
Urban Emmenegger
Publication date: 01-09-2019
Publisher: Springer Berlin Heidelberg
Keywords: Prostate Cancer
Dabigatran
Pharmacokinetics
Edoxaban
Anticoagulant
Direct Oral Anticoagulant
Prostate Cancer
Atrial Fibrillation
Apixaban
Warfarin
Direct Oral Anticoagulant
Low Molecular Weight Heparin
Rivaroxaban
Published in: Supportive Care in Cancer / Issue 9/2019
Print ISSN: 0941-4355
Electronic ISSN: 1433-7339
DOI: https://doi.org/10.1007/s00520-019-04816-y

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