Methotrexate-associated liver toxicity in a patient with breast cancer: case report and literature review

Neth J Med. 2002 Jun;60(5):216-22.


A patient with breast cancer developed severe asthenia, accompanied with progressively increasing transaminases, during adjuvant chemotherapy with CMF (cyclophosphamide, methotrexate and 5-fluorouracil). Additional blood tests and imaging were negative. A liver biopsy revealed a grade II toxic hepatitis. Because methotrexate was suspected to be the cause of the hepatotoxicity, the administration of this drug was stopped and mitoxantrone was given instead. A recovery of clinical symptoms and normalisation of the liver function tests was observed afterwards. In that sense, mitoxantrone appears to be a valuable alternative to methotrexate in cases of hepatotoxicity in patients with breast cancer. An overview of the literature regarding methotrexate hepatotoxicity is presented.

Publication types

  • Case Reports
  • Review

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Breast Neoplasms / drug therapy*
  • Chemical and Drug Induced Liver Injury / etiology*
  • Chemotherapy, Adjuvant
  • Female
  • Humans
  • Methotrexate / administration & dosage
  • Methotrexate / adverse effects*
  • Middle Aged
  • Mitoxantrone / administration & dosage


  • Mitoxantrone
  • Methotrexate