Single nucleotide polymorphisms to predict taxanes toxicities and effectiveness in cancer patients

Pharmacogenomics J. 2021 Aug;21(4):491-497. doi: 10.1038/s41397-021-00227-7. Epub 2021 Mar 1.

Abstract

Taxanes are used in the treatment of several solid tumours. Adverse events (AEs) might be influenced by single nucleotide polymorphisms (SNPs) in genes encoding proteins responsible for pharmacokinetic and pharmacodynamic. In this prospective, monocentric, observational study we explored the effect of SNPs in the main genes involved in taxanes metabolism and transport, on toxicity and efficacy in 125 patients (pts) treated with paclitaxel, nab-paclitaxel, or docetaxel for neoplasms. There was no statistically significant association between the investigated SNPs and AEs. The heterozygous genotype of CYP3A4*22 showed a trend of association with skin reactions in pts treated with paclitaxel and nab-paclitaxel (RR = 6.92; 95% CI 0.47, 99.8; p = 0.0766). CYP2C8*3/*4 variant carriers showed a trend of association with overall AEs in pts treated with paclitaxel and nab-paclitaxel (RR = 1.28; 95% CI 0.96, 1.67; p = 0.0898). No statistically significant relationship with treatment efficacy was found. ABCB1 3435TT showed a trend of association with a higher treatment response (RR = 0.22; 95% CI 0.03, 1.51; p = 0.0876). Despite the population was heterogeneous, CYP3A4*22 and CYP2C8 SNPs may influence paclitaxel and nab-paclitaxel toxicity and ABCB1 c.3435 may affect taxanes effectiveness, even if any statistically significant was found.

Publication types

  • Observational Study

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B / genetics
  • Adult
  • Aged
  • Aged, 80 and over
  • Albumins / therapeutic use
  • Cytochrome P-450 CYP3A / genetics
  • Docetaxel / therapeutic use
  • Female
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Neoplasms / drug therapy*
  • Neoplasms / genetics*
  • Paclitaxel / therapeutic use
  • Pharmacogenetics / methods
  • Polymorphism, Single Nucleotide / genetics*
  • Prospective Studies
  • Taxoids / adverse effects*
  • Taxoids / therapeutic use*

Substances

  • 130-nm albumin-bound paclitaxel
  • ATP Binding Cassette Transporter, Subfamily B
  • Albumins
  • Taxoids
  • Docetaxel
  • Cytochrome P-450 CYP3A
  • Paclitaxel