Octreotide Acetate Administration for Malignant Bowel Obstruction Induces Severe Bradycardia in Patients with Terminal Stage Cancer: Two Case Reports

Abstract

Dear Editor:Octreotide acetate has recently been used in the management of malignant bowel obstruction in patients with terminal stage cancer. 1 Bradycardia is a known side effect of octreotide acetate in carcinoid tumor and acromegaly and other clinical settings, but has not been previously reported in a case of terminal stage cancer. Bradycardia by octreotide acetate mostly occurs at the start of therapy. This report presents two rare cases in which bradycardia developed 6 and 12 days after the start of octreotide acetate administration in a patient with terminal stage cancer. Case 1A 44-year-old female patient was diagnosed with International Federation of Gynecology and Obstetrics (FIGO) stage IV b cervical cancer. She underwent radiotherapy and systemic chemotherapy. She developed malignant bowel obstruction after the progression of disease, and octreotide acetate (300lg/day) was started to treat the obstruction. Opioid was administered for pain control. No bradycardia occurred at the start of octreotide acetate administration. However, she was found to have severe bradycardia (30 beats/min) after 12 days of administration of the octreotide acetate. An electrocardiogram (ECG) showed normal sinus rhythm. The bradycardia was temporarily improved by the administration of atropine, although it recurred after several hours. The subsequent administration of isoproterenol hydrochloride rapidly improved the bradycardia. Case 2A 61-year-old female was diagnosed with FIGO stage II b cervical cancer. She underwent concurrent chemoradiotherapy, including brachytherapy. After recurrence of disease, she underwent systemic chemotherapy. After progression of the disease, she developed malignant bowel obstruction. Octreotide acetate administration was initiated, and opioid was administered for pain control. No bradycardia occurred at the start of octreotide acetate administration. However, after six days of administration, she was found to have severe bradycardia (*30 beats/min). An ECG showed normal sinus rhythm. The bradycardia was temporarily improved by administration of atropine, although it recurred after several hours. The subsequent administration of isoproterenol hydrochloride was necessary to improve the bradycardia.This is the first report of severe bradycardia occurring several days after the start of octreotide acetate administration for the management of the symptoms of malignant bowel obstruction in patients with terminal stage cancer. Octreotide acetate is an analogue of somatostatin, a hormone that is physiologically important for the control of cardiac impulse formation and conduction. 2 Bradycardia has been described as a side effect of octreotide acetate in other clinical settings, although infrequently. 3,4 Sinus bradycardia ( < 50 bpm) developed in 25% and dysrhythmias developed in 9% of acromegalic patients receiving octreotide acetate. 4 The mechanisms by which octreotide acetate can cause bradycardia remain unclear. Yuhico and colleagues recently reported that octreotide acetate causes asystolic even...