A retrospective study of cardiotoxicity of breast cancer patients treated with doxorubicin at Phrachomklao Hospital

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Lersak Prachuabaree
Sawitree Ket-aim

Abstract

Doxorubicin is chemotherapeutic agent in the standard regimen for the treatment of breast cancer. The major adverse drug reaction is cardiotoxicity. This study aimed to determine the incidence and risk-factors of congestive heart failure (CHF) in breast cancer patients treated with doxorubicin at Phrachomklao Hospital. Methods: This was a 10-year retrospective study of breast cancer patients treated with doxorubicin at Phrachomklao Hospital from January 1, 2008 to December 31, 2018. The data was collected from electronic medical records (EMR). A logistic regression analysis was used to determine factors associated with the development of CHF. Result: Two hundred thirteen patients were prescribed 574 doses of doxorubicin. The incidence of doxorubicin-induced congestive heart failure was 5.6% (12 cases, 0.0209 events per patient-dose of exposure), seven patients (3.29%) developed early-onset congestive heart failure and 5 patients (2.33%) developed late-onset congestive heart failure. The only significant risk factor for CHF was cumulative dose of doxorubicin. A cumulative dose over 300 mg/mm2 showed higher incidence of CHF compared to lower cumulative dose (< 300 mg/m2) (RR 4.48, 95% CI; 1.30-15.45, p= 0.01). The risk of CHF in patients undergoing hormone therapy was lower. Conclusion: The incidence of doxorubicin-induced CHF in breast cancer patients treated with doxorubicin at Phrachomklao Hospital was 5.6% within the first year. A cumulative dose greater than 300 mg/mm2 was a significant risk factor for developing heart failure. Close monitoring of cardiotoxicity should be performed in high risk patients, especially during the first year post treatment.

Article Details

Section
Pharmaceutical Practice

References

Adriana A, Giuseppina P, Francesco D, et al. Cardiotoxicity of Anticancer Drugs: The Need for Cardio-Oncology and Cardio-Oncological Prevention .JNCI. 2010; 102 (1):14–25, available: https://doi.org/10.1093/jnci/djp440

Armenian SH, Lacchetti C, Barac A, 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 Mar 10;35(8):893-911.

Bonadonna G, Valagussa P, Moliterni A, et al. Adjuvant cyclophosphamide, methotrexate, and fluorouracil in node-positive breast cancer: the results of 20 years of follow-up. N Engl J Med 1995; 332(14): 901-906.

Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2018;68:394-424.

Cardinale D, Colombo A, Bacchiani G, et al. Early detection of anthracycline cardiotoxicity and improvement with heart failure therapy. Circulation. 2015;131(22):1981-1988.

Chlebowski RT. Adriamycin (doxorubicin) cardiotoxicity: a review. West J Med. 1979;131(5):364-368.

Curigliano G, Cardinale D, Suter T, et al. Cardiovascular toxicity induced by chemotherapy, targeted agents and radiotherapy: ESMO Clinical Practice Guidelines. Ann Oncol. 2012;23 Suppl 7:vii155-vii166.

Dorr RT, Von-Hoff DD. Drug monographs. Cancer chemotherapy handbook. 2nd ed. Norwalk, Conneticut: Appleton and Lange; 1994.

Doyle JJ, Neugut AI, Jacobson JS, et al. Chemotherapy and cardiotoxicity in older breast cancer patients: a population-based study. J Clin Oncol. 2005;23(34):8597-8605.

Early Breast Cancer Trialists' Collaborative Group (EBCTCG). Long-term outcomes for neoadjuvant versus adjuvant chemotherapy in early breast cancer: meta-analysis of individual patient data from ten randomised trials. Lancet Oncol. 2018;19(1):27-39.

Gradishar WJ, Anderson BO, Balassanian R, et al. NCCN Guidelines Insights: Breast Cancer, Version 1.2017. J Natl Compr Canc Netw. (2017).

Hensley ML, Hagerty KL, Kewalramani T, et al. American Society of Clinical Oncology 2008 clinical practice guideline update: use of chemotherapy and radiation therapy protectants. J Clin Oncol. 2009;27(1):127-145

Jain D, Russell RR, Schwartz RG, et al. Cardiac complications of cancer therapy: Pathophysiology, identification, prevention, treatment, and future directions. Curr Cardiol Rep. 2017;19:36.

Kannan A, Janardhanan R. Hypertension as a risk factor for heart failure. Curr Hypertens Rep. 2014;16(7):447.

Keizer HG, Pinedo HM, Schuurhuis GJ, et al. Doxorubicin (adriamycin): a critical review of free radical-dependent mechanisms of cytotoxicity. Pharmacology & therapeutics 1990;47(2):219-231.

Khosrow-Khavar F, Filion K. B, Al-Qurashi S, et al. Cardiotoxicity of aromatase inhibitors and tamoxifen in postmenopausal women with breast cancer: a systematic review and meta-analysis of randomized controlled trials. Ann Oncol. 2017;28 (3) 487-496.

Lehrke M, Marx N. Diabetes Mellitus and Heart Failure. Am J Cardiol. 2017;120(1S):S37-S47.

Matsen CB, Neumayer LA. Breast cancer: a review for the general surgeon [published correction appears in JAMA Surg. 2013 Dec;148(12):1086]. JAMA Surg. 2013;148(10):971-979.

Myers C. The role of iron in doxorubicin-induced cardiomyopathy. Seminars in oncology 1998;25(suppl 10):10-14.

Pinder MC, Duan Z, Goodwin JS, et al., Giordano SH. Congestive heart failure in older women treated with adjuvant anthracycline chemotherapy for breast cancer. J Clin Oncol. 2007;25(25):3808-3815.

Plana JC, Galderisi M, Barac A, et al. Expert consensus for multimodality imaging evaluation of adult patients during and after cancer therapy: a report from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. J Am Soc Echocardiogr. 2014 Sep;27(9):911-39.

Seidman A, Hudis C, Pierri MK, et al. Cardiac dysfunction in the trastuzumab clinical trials experience, J Clin Oncol, 2002, vol. 20 5(pg. 1215-1221)

Suter TM, Ewer MS. Cancer drugs and the heart: importance and management. Eur Heart J. 2013;34(15):1102-1111.

Swain SM, Whaley FS, Ewer MS. Congestive heart failure in Patients treated with doxorubicin: a retrospective analysis of three trials. Cancer. 2003;97(11):2869-79.

Virani S, Bilheem S, Chansaard W, et al. National and subnational population-based incidence of cancer in Thailand: assessing cancers with the highest burdens. Cancers 2017;9:E108.

Von Hoff DD, Layard MW, Basa P, et al. Risk factor for doxorubicin induced congestive heart failure. Intern Med. 1979;91(5):710-7.

Weiss RB. Hypersensitivity reactions. In: Perry MC (ed). The chemotherapy source book, 3rd ed. Philadelphia: Lippincott Williams & Wilkin, 2001:436-52.