Two cases of severe liver injury possibly related to 5‐fluorouracil and calcium folinate

5-Fluorouracil (5-FU) is used to treat a variety of tumours, often in combinationwith calcium folinate. The activity of 5-FU is associated with the inhibition of thymidylate synthase (TS), with calcium folinate prolonging the inhibition of thymidylate synthase. 5-FU and calcium folinate havebeen shown to increase significantly 1-year survival in advanced colorectal cancer in a meta-analysis. Whereas 5-FUcausesmultisystem toxicity, severedrug-induced liver injury does not appear to have been described except after hepatic arterial infusion. In relation to combination therapy, a syndrome of ascites, hyperbilirubinaemia and hypoalbuminaemia, has been reported following 5-FU and N-phosphonacetyl-L-aspartate for the treatment of hepatic metastases. There appear to be no reports of severe liver injury following 5-FU and calcium folinate. We describe two cases of severe drug-induced liver injury in association with bolus i.v. 5-FU and calcium folinate. The first patient was a 66-year-old man who presented with jaundice 6 weeks after completing a 30-week course of once-weekly bolus i.v. 5-FU (750 mg) and calcium folinate (35 mg), for treatment of Duke’s C colonic carcinoma. The patient had liver function tests (LFT) within normal limits before commencing chemotherapy, when hewas not receiving anymedication. At presentation, LFT showed a hepatocellular picture, with increased alanine aminotransferase (ALT) 866 U/L, aspartate aminotransferase (AST) 644 U/L, bilirubin525 lmol/L, alkalinephosphatase (ALP) 170 U/L and c-glutamyltransferase (GGT) 114 U/L. The International Consensus Criteria classifies Letters to the Editor