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ORIGINAL ARTICLE
Year : 2017  |  Volume : 13  |  Issue : 6  |  Page : 961-963

Cardiotoxicity associated with bortezomib: A single-center experience


1 Department of Internal Medicine, HealthEast Care System, St. Paul, Minnesota, 55102, USA
2 Department of Research, HealthEast Care System, St. Paul, Minnesota, 55102, USA
3 Department of Data Science, HealthEast Care System, St. Paul, Minnesota, 55102, USA
4 Department of Oncology, HealthEast Care System, St. Paul, Minnesota, 55102, USA

Date of Web Publication13-Dec-2017

Correspondence Address:
Dr. Murali Krishna Gurram
45, 10th Street West, St. Paul, Minnesota 55102
USA
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0973-1482.172126

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 > Abstract 

Background: Studies evaluating the prevalence of cardiotoxicity associated with bortezomib are limited. We proposed this study to evaluate the prevalence of cardiotoxicity associated with bortezomib and its relation to multiple myeloma and other malignancies.
Materials and Methods: This is a retrospective, chart review study. Subjects who received bortezomib at the HealthEast care system for various oncologic conditions were evaluated after obtaining IRB approval.
Results: A total of 64 patients received bortezomib for various malignancies. Nine out of 64 (14%) patients developed cardiotoxicity during treatment with bortezomib, and the majority of these patients had a prior cardiac history and other cardiac risk factors. On further review, we did not find any significant causal relationship between these cardiac events and bortezomib.
Conclusion: Cardiotoxicity is probably not related to bortezomib, even though there are some case reports suggestive of cardiac events related to bortezomib. Our findings need to be confirmed in multicenter, prospective studies.

Keywords: Bortezomib, cardiotoxicity, multiple myeloma


How to cite this article:
Gurram MK, Pulivarthi S, Ehresmann K, Mathew J. Cardiotoxicity associated with bortezomib: A single-center experience. J Can Res Ther 2017;13:961-3

How to cite this URL:
Gurram MK, Pulivarthi S, Ehresmann K, Mathew J. Cardiotoxicity associated with bortezomib: A single-center experience. J Can Res Ther [serial online] 2017 [cited 2020 Feb 20];13:961-3. Available from: http://www.cancerjournal.net/text.asp?2017/13/6/961/172126


 > Introduction Top


Bortezomib (Velcade) is a proteasome inhibitor used in the treatment of relapsed or refractory multiple myeloma (MM) or as a first-line treatment of MM, and it has also been used in the treatment of solid tumors.[1],[2],[3] There are multiple case reports suggestive of cardiotoxicity associated with bortezomib.[4],[5],[6],[7],[8],[9] In one meta-analysis, which analyzed cardiotoxicity associated bortezomib treatment, they did not find any significant cardiotoxicity associated with bortezomib.[10] Another study reported that eight out of 69 (11.6%) patients who received bortezomib developed cardiac complications.[11] We proposed this study to evaluate cardiotoxicity associated with bortezomib and its relation to various malignancies and other comorbidities in a community hospital setting.


 > Materials and Methods Top


This is a retrospective, chart review study. Subjects who were 18 years or older and received bortezomib at the HealthEast care system from January 2005 to July 2014 for various oncologic conditions were evaluated after obtaining IRB approval. Patients who did not want to participate in the research (if they signed any forms stating their wish at the time of receiving chemotherapy) were excluded from the study. Data were collected using REDCap database. Age, gender, type of malignancy, prior chemotherapy, prior malignancy, other chemotherapy along with bortezomib, comorbidities, history of cardiovascular diseases, the number of cycles of bortezomib, route of administration, and cardiac workup (blood work and imaging studies) were collected. Cardiology consults notes and attending physician notes were also reviewed to evaluate the etiology of cardiac events.


 > Results Top


A total of 64 patients were evaluated. None of the patients were excluded from the study. [Table 1] shows the demographics of the study population. Among the study population, 64.1% were male and 35.9% were female. Age ranged from 35 to 94 years with a median age of 65.5 years. A total of 45 patients had MM, 16 patients had other malignancies/medical problems, two patients had MM with amyloidosis, and one patient had the possible polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome. 81.3% of the patients received other chemotherapy along with bortezomib. 12.5% of the patients had prior cancer diagnosis other than MM, and 26.6% received prior chemotherapy for MM and other malignancies. Nine out of 64 (14%) patients developed cardiac events during the treatment with bortezomib, five out of these nine patients continued to receive bortezomib after developing cardiac complications. [Table 2] demonstrates characteristics of the nine subjects who developed cardiotoxicity and their demographic profiles. Charts were reviewed thoroughly to identify the etiology of cardiac manifestations. The majority of these patients had a history of cardiac diseases such as atrial fibrillation (AF), coronary artery disease, congestive heart failure (CHF), and cardiovascular risk factors such as hypertension (HTN), diabetes mellitus (DM), hyperlipidemia, and smoking. On further review, we did not find any significant correlation between these cardiac events and treatment with bortezomib.
Table 1: Demographics of the study population

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Table 2: Detailed characteristic features of nine patients presented with cardiac events during the treatment with bortezomib

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 > Discussion Top


Cardiac complications associated with bortezomib have been reported in multiple case reports, but original research is limited on this topic.[4],[5],[6],[7],[8],[9] Foley et al. reported a case of myocardial scarring associated with bortezomib.[4] In four different case reports, one patient had complete heart block, another patient had ischemic heart disease, and two patients had heart failure associated with bortezomib.[5],[6],[7],[8] Heart failure was reported in another patient after treatment with bortezomib-containing chemotherapy regimen (bortezomib, cisplatin, and gemcitabine).[9] In a study by Enrico et al., eight out of 69 patients who received bortezomib developed cardiac complications, including heart failure, angina, and rhythm abnormalities.[11] In a systemic review and meta-analysis done by Xiao et al., they found no significant difference in cardiotoxicity between the patients who received bortezomib as compared to the control group.[10] In our study, nine out of 64 patients developed cardiac complications during treatment with bortezomib, and we found that none of these events were related to bortezomib. Two patients developed CHF and AF, two patients had ischemic heart disease, two patients had AF, one patient had ventricular tachycardia and CHF, one patient had CHF, and one patient had bradycardia. Of these patients, who developed cardiac complications, four were males and five were females, eight patients had MM, and one had Waldenstrom macroglobulinemia. Seven patients developed cardiac complications after receiving five or more cycles of bortezomib. All except one had a history of HTN, five patients had a prior cardiac history, six patients had a history of smoking, and two patients had a history of DM.


 > Conclusion Top


In our study, 14% of patients developed cardiac events during treatment with bortezomib. On further review, these patients had a prior cardiac history and other cardiovascular risk factors. We found that these cardiac events were not related to bortezomib. In conclusion, cardiotoxicity is probably not related to bortezomib, but this needs to be confirmed by large multicenter prospective studies. Our study is limited by small sample size, retrospective chart review, and single-center experience.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
 > References Top

1.
Richardson PG, Briemberg H, Jagannath S, Wen PY, Barlogie B, Berenson J, et al. Frequency, characteristics, and reversibility of peripheral neuropathy during treatment of advanced multiple myeloma with bortezomib. J Clin Oncol 2006;24:3113-20.  Back to cited text no. 1
[PUBMED]    
2.
Richardson PG, Xie W, Mitsiades C, Chanan-Khan AA, Lonial S, Hassoun H, et al. Single-agent bortezomib in previously untreated multiple myeloma: Efficacy, characterization of peripheral neuropathy, and molecular correlations with response and neuropathy. J Clin Oncol 2009;27:3518-25.  Back to cited text no. 2
[PUBMED]    
3.
Milano A, Perri F, Caponigro F. The ubiquitin-proteasome system as a molecular target in solid tumors: An update on bortezomib. Onco Targets Ther 2009;2:171-8.  Back to cited text no. 3
[PUBMED]    
4.
Foley PW, Hamilton MS, Leyva F. Myocardial scarring following chemotherapy for multiple myeloma detected using late gadolinium hyperenhancement cardiovascular magnetic resonance. J Cardiovasc Med (Hagerstown) 2010;11:386-8.  Back to cited text no. 4
    
5.
Dasanu CA. Complete heart block secondary to bortezomib use in multiple myeloma. J Oncol Pharm Pract 2011;17:282-4.  Back to cited text no. 5
    
6.
Bockorny M, Chakravarty S, Schulman P, Bockorny B, Bona R. Severe heart failure after bortezomib treatment in a patient with multiple myeloma: A case report and review of the literature. Acta Haematol 2012;128:244-7.  Back to cited text no. 6
    
7.
Gupta A, Pandey A, Sethi S. Bortezomib-induced congestive cardiac failure in a patient with multiple myeloma. Cardiovasc Toxicol 2012;12:184-7.  Back to cited text no. 7
    
8.
Takamatsu H, Yamashita T, Kotani T, Sawazaki A, Okumura H, Nakao S. Ischemic heart disease associated with bortezomib treatment combined with dexamethasone in a patient with multiple myeloma. Int J Hematol 2010;91:903-6.  Back to cited text no. 8
    
9.
Voortman J, Giaccone G. Severe reversible cardiac failure after bortezomib treatment combined with chemotherapy in a non-small cell lung cancer patient: A case report. BMC Cancer 2006;6:129.  Back to cited text no. 9
    
10.
Xiao Y, Yin J, Wei J, Shang Z. Incidence and risk of cardiotoxicity associated with bortezomib in the treatment of cancer: A systematic review and meta-analysis. PLoS One 2014;9:e87671.  Back to cited text no. 10
    
11.
Enrico O, Gabriele B, Nadia C, Sara G, Daniele V, Giulia C, et al. Unexpected cardiotoxicity in haematological bortezomib treated patients. Br J Haematol. 2007;138:396-7.  Back to cited text no. 11
    



 
 
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