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.

• Authors: Yoshinao Ozaki, Hirotaka Imamaki, Aki Ikeda, Mitsuaki Oura, Shunsaku Nakagawa, Taro Funakoshi, Shigeki Kataoka, Yoshitaka Nishikawa, Takahiro Horimatsu, Atsushi Yonezawa, Takeshi Matsubara, Motoko Yanagita, Manabu Muto, Norihiko Watanabe
• Journal: Cancer chemotherapy and pharmacology (Cancer Chemother Pharmacol) Vol. 86 Issue 5 Pg. 693-699 (11 2020) ISSN: 1432-0843 [Electronic] Germany
• PMID: 33011861 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antimetabolites, Antineoplastic
• Fluoroacetates
• beta-Alanine
• alpha-fluoro-beta-alanine
• Ammonia
• fluoroacetic acid
• Fluorouracil

Topics

• Aged, 80 and over
• Ammonia (blood)
• Antimetabolites, Antineoplastic (administration & dosage, adverse effects, blood, metabolism)
• Drug Administration Schedule
• Fluoroacetates (blood, metabolism)
• Fluorouracil (administration & dosage, adverse effects, blood, metabolism)
• Humans
• Hyperammonemia (blood, chemically induced, diagnosis, therapy)
• Male
• Renal Dialysis
• Stomach Neoplasms (drug therapy)
• Time Factors
• Treatment Outcome
• beta-Alanine (analogs & derivatives, blood, metabolism)