Irinotecan inducing sinus pause bradycardia in a patient with small round cell cancer

  1. Tanveer Ahmad Mir 1,
  2. Ahmed S Yassin 1,
  3. Eric Joseph Denha 1,
  4. Raad Al Shaikhli 1,
  5. Ali Rahim 1,
  6. Sabah Ambreen 2 and
  7. Prateek Lohia 1
  1. 1 Internal Medicine, Detroit Medical Center, Wayne State University, Detroit, Michigan, USA
  2. 2 Independent Researcher, Detroit, MI, USA
  1. Correspondence to Dr Tanveer Ahmad Mir; gr6723@wayne.edu

Publication history

Accepted:21 Dec 2019
First published:31 May 2020
Online issue publication:31 May 2020

Case reports

Case reports are not necessarily evidence-based in the same way that the other content on BMJ Best Practice is. They should not be relied on to guide clinical practice. Please check the date of publication.

Abstract

Irinotecan is a novel anticancer drug that has worked wonders in combination with other anticancer drugs. It can be used as a single chemotherapy agent in colonic cancer treatment or in combination with 5-fluorouracil. Irinotecan has been found a better salvage therapy in patients who are resistant to 5-fluorouracil. It is also used in combination with cisplatin and other drugs for cancers such as pleural mesothelioma, Ewing’s sarcoma, lung cancer and others, and has helped reduce tumour burden. Irinotecan is generally associated with gastrointestinal side effects including nausea, vomiting and diarrhoea, while cardiovascular toxicity (5%) has been reported mainly as vasodilatation and possible bradycardia with no known incidence. A case was reported in 1998 by Miya et al of a 65-year-old man with bradycardia which was managed with atropine without modifications in the dosage of irinotecan or in the rate of infusion. We report a case of a patient with small round cell cancer who presented with sinus pause bradycardia after infusion with irinotecan. The patient was managed with atropine during chemotherapy.

Background

Although irinotecan is a novel drug generally associated with gastrointestinal adverse drug reactions, we present a case of sinus pause bradycardia after infusion with irinotecan.

Case presentation

A 26-year-old woman with previous medical conditions that include undifferentiated small round cell sarcoma of the left proximal anterior tibial compartment (Ewing’s-like sarcoma) and metastasis to the right and left lung after resection of the left lower lobe was recently started on irinotecan and temozolomide. She had no complaints prior to chemotherapy infusion and was in her usual state of health. Postchemotherapy she developed bilious vomiting with associated dizziness, which was managed conservatively with ondansetron and Ativan. She denied any other gastrointestinal complaints, including abdominal pain, diarrhoea or bloating. Also, on further questioning she admitted to decreased fluid intake by mouth and occasional light-headedness. She had no personal or family history of any cardiac disease.

On examination she was noted to have hypotension with a blood pressure of 94/60 mm Hg and bradycardia with a pulse rate of 48 beats per minute, which was irregularly irregular. She was awake, alert and oriented ×3. Cardiac examination revealed no murmurs, peripheral oedema or any jugular venous distension. All laboratory results were normal, as given in the Investigations section.

ECG before chemotherapy showed normal sinus rhythm (figure 1). Repeat ECG was done, this time showing bradycardia with sinus pauses of less than a second (figure 2). Echocardiography before chemotherapy was normal with ejection fraction of more than 60%.

Figure 1

Baseline electrocardiogram before irinotecan.

Figure 2

Electrocardiogram after infusion with irinotecan.

The patient was managed with atropine and her bradycardia resolved. She completed her chemotherapy with no other complaints and was not managed with any antiarrhythmic medications.

Investigations

  • Sodium: 141 meq/L.

  • Bicarbonate: 24 meq/L.

  • Blood urea nitrogen: 12.

  • Magnesium: 2.2 mg.

  • Potassium: 4.2 meq/L.

  • Anion gap: 9.

  • Creatinine: 0.70 mg.

  • Haemoglobin: 11.3 g/L.

  • Chloride: 108 meq/L.

  • Glucose: 128 mg.

  • Calcium 7.7 (corrected 8.9) mg.

  • Thyroid stimulating hormone: 3.2 units.

Outcome and follow-up

Postchemotherapy the patient had no further episodes of bradycardia and is being followed as an outpatient. Her vitals, including pulse rate, are within normal limits.

Discussion

Irinotecan, or 7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxycamptothecin, is a derivative of camptothecin, a topoisomerase I inhibitor, and its metabolite 7-ethyl-10-hydroxycamptothecin (CPT-11) has a potent antitumour activity in vivo.1

Irinotecan has been used as cancer treatment for decades and is mostly used as a combination chemotherapy drug. Diarrhoea and upper gastrointestinal symptoms are the most common adverse effects, in addition to haematological side effects such as leucopenia and thrombocytopaenia, as reported in a Japanese phase II study2 and in another recent study by Nakano et al.3 Cardiovascular toxicity has been reported mainly as vasodilatation and possible bradycardia, especially during infusions, with no known incidence as per data given in drug reference in uptodate 2019.4 Miya et al 5 reported bradycardia on electrocardiogram (EKG) revealing sinus pauses similar to our patient. Irinotecan has been used as an alternative chemotherapy agent in patients who developed cardiotoxicity from 5-fluorouracil, without any added cardiac effects.6 Bradycardia induced by irinotecan is very rare.

The mechanism of bradycardia induced by irinotecan is not understood. In a previous case report by Miya et al,5 cholinergic side effects were suggested. Atropine helps manage bradycardia, suggesting its cholinergic effect. Our patient was dehydrated due to poor oral intake and nausea and vomiting. In spite of being dehydrated and hypotensive, the patient had bradycardia at 48 beats per minute. The reproduction of symptoms and sinus pauses on electrocardiography, while on irinotecan infusion in a patient with no previous abnormal cardiac history, confirms sinus pauses are related to irinotecan. We do not think the patient’s condition was secondary to ondansetron because it was not given by intravenous route and the patient’s classic presentation of sinus block has not been reported with ondansetron. Ondansetron causes QT prolongation and atrial fibrillation.7

Utmost vigilance is required during infusion especially in elderly patients with underlying sinus node diseases.

Learning points

  • Irinotecan has cardiotoxic effects, presenting as sinus block.

  • Cardiac monitoring is important during irinotecan use.

  • Atropine is helpful for treatment continuation.

  • Patients can be symptomatic of bradycardia, so fall precautions during the treatment in hospital should be used.

  • Bradycardia stops once use of irinotecan is stopped.

Footnotes

  • Contributors TAM, ASY, EJD, RAS, AR, SA and PL: compiling the data, case review, and formatting and final approval.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Patient consent for publication Obtained.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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