5-Fluorouracil-induced Pericarditis: Uncommon Cardiac Toxicity with a Common Cancer Drug

Dear Editor, Here, we present a case study of a 31-year-old man with no known medical risk factors and with an Eastern Cooperative Oncology Group performance status 1, who was diagnosed as a case of right-sided carcinoma buccal mucosa (squamous cell) with stage IV (cT4aN3bM0) as per American Joint Committee on Cancer 8th and was planned for induction chemotherapy in the form of TPF regimen (a combination of Docetaxel 75 mg/m2 Day 1, cisplatin 75 mg/m2 Day 1, and 5-fluorouracil [5-FU] 750 mg/m2 Day 1–5). 5-FU was given as a continuous infusion over 5 days. A pre-chemotherapy cardiac evaluation was not done as it was not a routine practice and was not supposed to be done on a young, fit man with no known medical risk factors. The initial 4 days of chemotherapy were uneventful. On the 5th day, the patient developed a complaint of chest pain, which was insidious in onset, dull in character, intermittent, radiating to the back and difficult to localise. It was aggravated on lying down and relieved on sitting up. It was more during inspiration and further aggravated by deep breaths. Along with this, the patient had a single episode of vomiting and generalised weakness. There was no complaint of fever or loose stools. Vitals were charted as blood pressure 106/64 mmHg and pulse rate was 136/min with maintained oxygen saturation on room air. On auscultation, a scratchy sound was heard (likely pericardial rub) with normal breath sounds. On the symptoms mentioned above and signs, differential diagnoses included myocardial infarction, pericarditis or myocarditis. All routine blood investigations were within normal limits, including complete blood count and renal and liver function tests with erythrocyte sedimentation rate, C-reactive protein and Trop T. Only Pro B-type natriuretic peptide was raised, and electrocardiogram (ECG) showed widespread ST elevation with PR depression. Chest X-ray appeared normal. However, echocardiography could not be done due to logistic issues. Based on the typical clinical features, especially the type of pain (along with associated aggravating and relieving factors) and correlating ECG findings, a diagnosis of pericarditis was considered, and the patient was given tablet aspirin 1000 mg every eight hourly and tablet prednisone 0.2 mg/kg once a day. He got complete symptomatic relief within 2 days and continued the maintenance dose for a week. This adverse drug reaction was reported to the pharmacovigilance centre in the hospital, which was further reported to the Pharmacovigilance Programme of India monitoring centre. DISCUSSION 5-FU is a synthetic fluoropyrimidine antimetabolite commonly used for upper and lower gastrointestinal tract, head and neck and breast cancer. It is administered as a daily bolus and/or continuous infusion over 24 h, lasting 4/5 days per individual regimen. Haematological and gastrointestinal toxicities due to dose schedules are common; thus, preventive and curative measures are always taken. Less common toxicities are neurological and cardiovascular. 5-FU has the second highest incidence of cardiotoxicity after anthracyclines. Among the cardiovascular toxicities, the most common are ECG changes, arrhythmia and myocardial infarction. Pericarditis, although a rare side effect, has been reported in a few case studies in the literature.[1,2] In a study by Schöber etal., it was analysed that the incidence of cardiotoxicity was 15.1% in patients with a history of ischaemic heart disease and 1.5% in those without a history of cardiac disease.[3] The risk of cardiotoxicity is higher with continuous infusion than with bolus injection.[4] As pre-existing ischaemic heart disease is a significant risk factor for 5-FU-induced cardiotoxicity, and just like for anthracyclines, cardiac evaluation should be done, and cardiac clearance should be obtained before its administration. Although these toxicities are encountered less commonly, they can be life-threatening. Fortunately, most of the 5-FU-induced cardiotoxicity is reversible, and in the case of pericarditis, administration of nonsteroidal anti-inflammatory drugs with discontinuation of 5-FU is the mainstay of treatment. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given his consent for his images and other clinical information to be reported in the journal. The patient understands that his name and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.