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ANALYTICAL REPORT
Year : 2012  |  Volume : 8  |  Issue : 3  |  Page : 442-444

Acute non-ST elevation myocardial infarction following paclitaxel administration for ovarian carcinoma: A case report and review of literature


1 Department of Medical Oncology, Tata Memorial Hospital, Mumbai, India
2 Department of Surgical Oncology, Tata Memorial Hospital, Mumbai, India

Date of Web Publication17-Nov-2012

Correspondence Address:
Sudeep Gupta
Department of Medical Oncology, Tata Memorial Hospital, Mumbai - 400012
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0973-1482.103530

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 > Abstract 

We report a case of an acute non-ST elevation myocardial infarction (AMI) induced by paclitaxel in a patient with ovarian cancer. A 45-year-old premenopausal lady without any co-morbidity was started on the first cycle of neoadjuvant chemotherapy with paclitaxel-based regimen for advanced stage ovarian cancer. The patient developed chest pain 3 h after paclitaxel infusion with characteristic electrocardiographic changes of antero-apical myocardial infarction. The patient recovered on conservative medical management with reversion of electrocardiogram (ECG) changes. Cardiac ischemia and myocardial infarction, possibly due to coronary vasospasm, are rare adverse effects of paclitaxel with reported incidence of 0.26%. We have reported a case of paclitaxel-induced myocardial infarction with reversible cardiac dysfunction. The possibility of myocardial infarction should be considered in patients who develop chest pain or other symptoms after paclitaxel infusion.

Keywords: Myocardial infarction, neoadjuvant chemotherapy, ovarian carcinoma, paclitaxel


How to cite this article:
Shah K, Gupta S, Ghosh J, Bajpai J, Maheshwari A. Acute non-ST elevation myocardial infarction following paclitaxel administration for ovarian carcinoma: A case report and review of literature. J Can Res Ther 2012;8:442-4

How to cite this URL:
Shah K, Gupta S, Ghosh J, Bajpai J, Maheshwari A. Acute non-ST elevation myocardial infarction following paclitaxel administration for ovarian carcinoma: A case report and review of literature. J Can Res Ther [serial online] 2012 [cited 2018 Oct 20];8:442-4. Available from: http://www.cancerjournal.net/text.asp?2012/8/3/442/103530


 > Introduction Top


Paclitaxel is an anticancer agent used for the treatment of breast, ovarian and other cancers. [1] The major side-effects of this drug are bone marrow suppression, alopecia, polyneuropathy and cardiac toxicities. [2] The cardiac toxicities include asymptomatic bradycardia, atrioventricular conduction blocks, atrial arrhythmias, left bundle branch block, ventricular tachycardia, congestive cardiac failure and fatal myocardial infarction. [3] Myocardial infarction is a serious and life-threatening adverse effect that has rarely been reported with paclitaxel use. [4]


 > Case Report Top


A 45-year-old non-diabetic, non-hypertensive premenopausal woman with no history of coronary heart disease presented with a history of abdominal distention in January 2011. Computed tomography (CT) scan of the abdomen and pelvis revealed a large abdominopelvic solid-cystic mass with an indeterminate hypodense liver mass that was considered to be a cyst. The CA-125 was elevated to 597 U/ml. She was suspected to have advanced stage epithelial ovarian cancer. She underwent exploratory laporotomy at another hospital and was found to have unresectable pelvic tumor adherent to adjacent bowel and urinary bladder. Surgery was abandoned after an omental biopsy, the histopathology of which revealed metastatic poorly differentiated adenocarcinoma consistent with primary cancer in the ovary. The baseline ECG was normal. A plan was made to treat her with three cycles of neoadjuvant chemotherapy (NACT) with paclitaxel 175 mg/m 2 on Day 1 and carboplatin AUC-6 on Day 2 followed by surgery.

The patient received intravenous ondansetron 8 mg, dexamethasone 8 mg, ranitidine 50 mg and promethazine 12.5 mg prior to the first cycle of NACT. She developed acute onset left-sided heaviness in the chest after the completion of 3-h paclitaxel infusion that was associated with perspiration and breathlessness. On examination the heart rate was 100 per min and regular, blood pressure was 170/100, respiratory rate was 28 per min and oxygen saturation was 96% on room air. She was started on oxygen at low flow rate. The ECG showed ST and T depression in leads V1, V2 and AVL [Figure 1]. She was immediately administered ecosprin and isosorbide dinitrate. Repeat ECG after 2 h showed progression of ST and T depression in V1, V2, V3 and AVL and reciprocal changes in leads I, II, III and V4-V6, suggestive of acute anterior apical wall myocardial infarction (AMI) [Figure 1]. The troponin T test was positive. Complete blood count, liver function tests, renal function tests and electrolytes were within normal limits. Transthoracic echocardiography showed hypokinesia of the lower interventricular septum, adjacent anterior wall and entire apical wall with depressed left ventricular systolic function and a left ventricular ejection fraction of 35 per cent. A diagnosis of acute myocardial infarction (AMI) induced by paclitaxel was made. She was treated with subcutaneous low molecular weight heparin, ecosprin, clopidogrel, atorvastatin, ramipril and metoprolol. Serial ECG was monitored. The clinical situation of the patient progressively improved with resolution of symptoms. The ECG reverted to normal after five days [Figure 1]. Repeat echocardiography after 10 days showed no regional wall motion abnormality with fair LV systolic function and a left ventricular ejection fraction of 50-55%. She was discharged from the hospital after 10 days. Coronary artery angiography was not done at this time since the patient had advanced stage malignancy and was planned only for medical management of the cardiac event. The patient received two more cycles of neoadjuvant chemotherapy at three-week intervals with single agent carboplatin, uneventfully. The repeat CA-125 after the third cycle of chemotherapy declined to 412 u/ml but the CT scan revealed increase in liver hypodense masses, new lung nodule and stable pelvic mass. In view of primary platinum refractoriness with poor outcome, cancer-directed therapy was abandoned and she was taken up for palliative care.
Figure 1: Serial electrocardiograms, Panel (a) 15 min after onset of symptoms, (b) 24 h after symptoms, (c) 5 days after onset of symptoms

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 > Discussion Top


This report describes a patient with ovarian cancer who developed paclitaxel-induced acute myocardial infarction. The complete reversibility of cardiac function in our patient suggests the possibility of coronary vasospasm induced by paclitaxel. [5] The mechanisms by which paclitaxel causes cardiac abnormalities, especially myocardial damage, are not well understood. There have been previous case reports of paclitaxel-induced fatal myocardial infarction (MI) in a patient with metastatic breast cancer. [4] and acute myocardial ischemia in a patient with metastatic ovarian carcinoma. [6] To the best of our knowledge there have been six previous reports of myocardial infarction either during or after paclitaxel infusion. [4],[5],[6],[7]

The adverse cardiac events include asymptomatic sinus bradycardia in up to 30% of patients, arrhythmias including AV conduction block, left bundle branch block, ventricular premature contractions and ventricular tachycardia in 5% of patients and ischemic manifestations. In several studies containing more than 100 patients the incidence of paclitaxel-induced cardiac toxicity has been between 0-4%. [2] It is also difficult to distinguish between the cardiac toxicity of paclitaxel versus that of the cremaphor formulation in which it is suspended. [3] Cremaphor, via the induction of histamine release, stimulates H1 and H2 receptors leading to increased myocardial oxygen demand, coronary vasoconstriction and chronotropic effects. Furthermore, the H2 antagonists that are used as premedication can themselves lead to cardiac arrhythmias particularly in patients with advanced age, severe systemic illness and renal dysfunction. Oncologists should be alert regarding the potential cardiac risks, particularly in first-line chemotherapy of epithelial ovarian carcinoma in patients with pre-existing heart disease or risk factors. [8]

In addition, paclitaxel is being combined with cardiac toxic agents such as anthracyclines in breast cancer. The enhanced risk of cardiac toxicity with this combination is probably related to a pharmacokinetic interaction in which cremophor lowers the renal and hepatic clearance of anthracyclines, resulting in their increased plasma levels. [9] An alternative hypothesis suggests that taxanes stimulate formation of doxorubicinol (toxic metabolite of doxorubicin) in the heart. [10] It is thus recommended to administer anthracyclines prior to paclitaxel, separate the infusions by at least 4h and/or limit the cumulative doxorubicin dose to 380 mg/m 2 . [9],[10]

In summary, myocardial damage secondary to paclitaxel infusion is a serious and life-threatening adverse effect and oncologists and nurses using this drug must be cognizant of this toxicity.

 
 > References Top

1.McGuire WP, Rowinsky EK, Rosenshein NB, Grumbine FC, Ettinger DS, Armstrong DK, et al. Taxol: A unique antineoplastic agent with significant activity in advanced ovarian epithelial neoplasms. Ann Intern Med 1989;111:273-9.  Back to cited text no. 1
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2.Rowinsky EK, Gilbert MR, McGuire WP, Noe DA, Grochow LB, Forastiere AA, et al. Sequences of taxol and cisplatin: A Phase I and pharmacologic study. J Clin Oncol 1991;9:1692-703.  Back to cited text no. 2
    
3.Arbuck SG, Strauss H, Rowinsky E, Christian M, Suffness M, Adams J, et al. A reassessment of cardiac toxicity associated with taxol. J Natl Cancer Inst Monogr 1993;15:117-30.  Back to cited text no. 3
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4.Hekmat E. Fatal myocardial infarction potentially induced by paclitaxel. Ann Pharmacother 1996; 30:1110-2.  Back to cited text no. 4
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5.Nguyen-Ho P, Kleiman NS, Verani MS. Acute myocardial infarction and cardiac arrest in a patient receiving paclitaxel. Can J Cardiol 2003; 19:300-2.  Back to cited text no. 5
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6.Schrader C, Keussen C, Bewig B, von Freier A, Lins M. Symptoms and signs of an acute myocardial ischemia caused by chemotherapy with Paclitaxel (Taxol) in a patient with metastatic ovarian carcinoma. Eur J Med Res 2005;10:498-501.  Back to cited text no. 6
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7.Park SH, Byon JS, Lee SW, Lee SJ, Jin DK, Shin WY. Coronary Artery Thrombosis Associated With Paclitaxel in Advanced Ovarian Cancer. Korean Circ J 2009;39:124-7.  Back to cited text no. 7
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8.Pai VB, Nahata MC. Cardiotoxicity of chemotherapeutic agents: Incidence, treatment and prevention. Drug Saf 2000;22:263-302.  Back to cited text no. 8
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9.Gianni L, Munzone E, Capri G, Fulfaro F, Tarenzi E, Villani F, et al. Paclitaxel by 3-hour infusion in combination with bolus doxorubicin in women with untreated metastatic breast cancer: High antitumor efficacy and cardiac effects in a dose-finding and sequence-finding study. J Clin Oncol 1995;13:2688-99.  Back to cited text no. 9
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10.Barrett-Lee PJ, Dixon JM, Farrell C, Jones A, Leonard R, Murray N, et al. Expert opinion on the use of anthracyclines in patients with advanced breast cancer at cardiac risk. Ann Oncol 2009;20:816-27.  Back to cited text no. 10
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