Successful management of hyperammonemia with hemodialysis on day 2 during 5-fluorouracil treatment in a patient with gastric cancer: a case report with 5-fluorouracil metabolite analyses

Abstract

Purpose Hyperammonemia is an important adverse event associated with 5-fluorouracil (5FU) from 5FU metabolite accumulation. We present a case of an advanced gastric cancer patient with chronic renal failure, who was treated with 5FU/leucovorin (LV) infusion chemotherapy (2-h infusion of LV and 5FU bolus followed by 46-h 5FU continuous infusion on day 1; repeated every 2 weeks) and developed hyperammonemia, with the aim of exploring an appropriate hemodialysis (HD) schedule to resolve its symptoms. Methods The blood concentrations of 5FU and its metabolites, α-fluoro-β-alanine (FBAL), and monofluoroacetate (FA) of a patient who had hyperammonemia from seven courses of palliative 5FU/LV therapy for gastric cancer were measured by liquid chromatography–mass spectrometry. Results On the third day of the first cycle, the patient presented with symptomatic hyperammonemia relieved by emergency HD. Thereafter, the 5FU dose was reduced; however, in cycles 2–4, the patient developed symptomatic hyperammonemia and underwent HD on day 3 for hyperammonemia management. In cycles 5–7, the timing of scheduled HD administration was changed from day 3 to day 2, preventing symptomatic hyperammonemia. The maximum ammonia and 5FU metabolite levels were significantly lower in cycles 5–7 than in cycles 2–4 (NH3 75 ± 38 vs 303 ± 119 μg/dL, FBAL 13.7 ± 2.5 vs 19.7 ± 2.0 μg/mL, FA 204.0 ± 91.6 vs 395.9 ± 12.6 ng/mL, mean ± standard deviation, all p < 0.05). After seven cycles, partial response was confirmed. Conclusion HD on day 2 instead of 3 may prevent hyperammonemia in 5FU/LV therapy.

A case of acute hyperammonemic encephalopathy after initiation of 5-fluorouracil chemotherapy

“…Further studies regarding the risk of fluoroacetate accumulation could determine best practices in safely administering 5-FU to patients with renal failure. [6] Our patient became encephalopathic following her initial 5-FU administration with a dose of 4105 mg; however, she showed improvement within 2 days following discontinuation of the infusion. e immediate recovery supports the "5-FU catabolite type, " where the catabolic pathways are still intact; however, it is the inadequate excretion of 5-FU catabolites and the administration of 5-FU that leads to the encephalopathy seen in our patient.…”

“…[3,5] A few case reports of patients with dialysis-dependent renal failure who developed hyperammonemic encephalopathy following 5-FU treatment show increased blood levels of fluoroacetate during episodes of encephalopathy, and the increased risk of hyperammonemia in patients with renal failure supports a causative association between fluoroacetate accumulation and this adverse event. [5,6] 5-FU has not traditionally been doseadjusted for patients with renal failure as the drug is primarily metabolized in the liver. Further studies regarding the risk of fluoroacetate accumulation could determine best practices in safely administering 5-FU to patients with renal failure.…”