Pharmacogenetic impact of docetaxel on neoadjuvant treatment of breast cancer patients

Pharmacogenomics. 2018 Nov;19(16):1259-1268. doi: 10.2217/pgs-2018-0080. Epub 2018 Sep 10.

Abstract

Aim: This study aimed to investigate the effect of CYP3A4 and CYP3A5 genotypes on clinical outcomes of docetaxel treatment.

Patients & methods: In the PROMIX trial, 150 breast cancer patients received docetaxel preoperatively. CYP3A4 and CYP3A5 genotype combinations were transformed into total CYP 3A phenotypes.

Results: Seven patients were characterized as poor metabolizer (PM), 22 patients as extensive metabolizer and 121 patients as intermediate metabolizer. The frequency of grade 3/grade 4 adverse events was higher in the PM group (p = 0.002). One PM subject who basically lacked enzyme activity died from typhlitis. Total 45 recurrences were reported after a median of 5-year follow-up; none of these was PM.

Conclusion: The allelic variants CYP3A4*22 and CYP3A5*3 contribute to the interpatient variations of docetaxel.

Keywords: breast cancer; docetaxel; personalized medicine; pharmacogenetics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Alleles
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / genetics*
  • Cytochrome P-450 CYP3A / genetics
  • Docetaxel / therapeutic use*
  • Female
  • Genotype
  • Humans
  • Middle Aged
  • Neoadjuvant Therapy / methods
  • Pharmacogenetics / methods
  • Pharmacogenomic Testing

Substances

  • Docetaxel
  • Cytochrome P-450 CYP3A