Severe and prolonged cyclophosphamide-induced hepatotoxicity in a breast cancer patient carrying a CYP2B6*7 variant

Pharmacogenomics. 2019 Nov;20(16):1119-1124. doi: 10.2217/pgs-2019-0093. Epub 2019 Nov 5.

Abstract

As a widely used alkylating agent, cyclophosphamide often leads to various toxicities. Severe hepatotoxicity has been rarely reported in breast cancer patients receiving chemotherapy containing cyclophosphamide. Differences in cyclophosphamide metabolism may contribute to variability in adverse events of patients. Here, we report on a case of a 68-year-old Chinese female with breast cancer who experienced severe and prolonged hepatotoxicity induced by cyclophosphamide. Pharmacogenetic tests showed that she was a carrier of CYP2B6*7 allele and this is the first case of a CYP2B6*7 variant in the Han Chinese population so far reported. In addition, the patient was also a carrier of an ALDH3A1*2 variant potentially contributing to the occurrence of hepatotoxicity. CYP2B6 and ALDH3A1 genotyping may play a role in guiding cyclophosphamide therapy.

Keywords: ALDH3A1 genotype; CYP2B6 genotype; cyclophosphamide; hepatotoxicity.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aldehyde Dehydrogenase / genetics
  • Alleles
  • Breast Neoplasms / complications
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / genetics
  • Breast Neoplasms / pathology
  • Chemical and Drug Induced Liver Injury / etiology
  • Chemical and Drug Induced Liver Injury / genetics*
  • Chemical and Drug Induced Liver Injury / pathology
  • Cyclophosphamide / administration & dosage
  • Cyclophosphamide / adverse effects*
  • Cytochrome P-450 CYP2B6 / genetics*
  • Female
  • Genotype
  • Humans
  • Liver / drug effects

Substances

  • Cyclophosphamide
  • CYP2B6 protein, human
  • Cytochrome P-450 CYP2B6
  • ALDH3A1 protein, human
  • Aldehyde Dehydrogenase