The role of S-adenosyl methionine in preventing FOLFOX-induced liver toxicity: a retrospective analysis in patients affected by resected colorectal cancer treated with adjuvant FOLFOX regimen

Expert Opin Drug Saf. 2011 May;10(3):345-9. doi: 10.1517/14740338.2011.562888. Epub 2011 Mar 15.

Abstract

Background: Hepatic toxicity is often related to chemotherapy agent administration, and it represents one of the principal causes of dose reduction and chemotherapy delays or discontinuation. S-Adenosyl methionine (AdoMet) supplementation is effective in the treatment of a variety of liver injuries, but it has never been evaluated in the prevention of chemotherapy-induced liver damage.

Patients and methods: A total of 105 patients affected by resected colorectal cancer (CRC) were enrolled. Forty-five were treated with FOLFOX IV adjuvant regimen without administering AdoMet, 60 were treated with the same regimen plus supplementation with AdoMet. Liver enzyme levels were assessed before starting the treatment and every therapy cycle. Liver toxicity, chemotherapy course delays, discontinuations and dose reductions due to liver toxicity were recorded.

Results: Aspartate aminotransferase (AST) (p < 0.001), alanine transaminase (ALT) (p = 0.003), bilirubin (p = 0.04) and gamma-glutamyltransferase (γ-GT) (p = 0.002) median level at the end of adjuvant therapy were significantly lower in patients treated with Adome. Patients supplemented with AdoMet experimented a lower grade of liver toxicity (p = 0.002) and had a reduced need of course delay (p < 0.0001) and dose reduction (p = 0.031).

Conclusions: The results of our study demonstrate a protective effect of AdoMet supplementation in patients affected by resected CRC treated with FOLFOX IV adjuvant regimen.

MeSH terms

  • Adult
  • Aged
  • Alanine Transaminase / metabolism
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Aspartate Aminotransferases / metabolism
  • Bilirubin / metabolism
  • Chemical and Drug Induced Liver Injury / enzymology
  • Chemical and Drug Induced Liver Injury / etiology*
  • Chemical and Drug Induced Liver Injury / prevention & control*
  • Chemotherapy, Adjuvant
  • Colorectal Neoplasms / drug therapy*
  • Female
  • Fluorouracil / administration & dosage
  • Fluorouracil / adverse effects
  • Humans
  • Leucovorin / administration & dosage
  • Leucovorin / adverse effects
  • Liver / drug effects
  • Liver / enzymology
  • Male
  • Middle Aged
  • Organoplatinum Compounds / administration & dosage
  • Organoplatinum Compounds / adverse effects
  • Retrospective Studies
  • S-Adenosylmethionine / therapeutic use*
  • gamma-Glutamyltransferase / metabolism

Substances

  • Organoplatinum Compounds
  • S-Adenosylmethionine
  • gamma-Glutamyltransferase
  • Aspartate Aminotransferases
  • Alanine Transaminase
  • Leucovorin
  • Bilirubin
  • Fluorouracil

Supplementary concepts

  • Folfox protocol