Gene single nucleotide polymorphism accumulation improves survival in advanced head and neck cancer patients treated with weekly paclitaxel

Laryngoscope. 2009 Aug;119(8):1484-90. doi: 10.1002/lary.20254.

Abstract

Objectives/hypothesis: Single nucleotide polymorphisms (SNPs) of certain genes involved in drug metabolism correlate with survival.

Methods: We evaluated the presence of SNPs in six genes (CYP2C8, GSTT1, GSTP1, MDR1-57, MDR1-62, and ERCC1) and the response rate (RR), time to progression (TTP), and overall survival (OS) of advanced head and neck cancer patients treated with weekly paclitaxel.

Results: SNPs in CYP2C8, MDR1-57, and MDR1-62 genes were more frequent than wild-type genes in our patients. RR was 45% (21/47), and median TTP in responders was 5.1 months. OS for all patients was 5.6 months. Response was higher in SNPs of MDR1-62, MDR1-57, or in two or more accumulated genes than in those with wild-type genes. OS was significantly longer in patients with two or more accumulated SNPs (P = .039).

Conclusions: Response rate and OS were significantly higher in patients with two or more accumulated SNPs.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Analysis of Variance
  • Confidence Intervals
  • Disease-Free Survival
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Endonucleases / genetics
  • Female
  • Gene Expression Regulation, Neoplastic
  • Genetic Markers / genetics*
  • Head and Neck Neoplasms / drug therapy*
  • Head and Neck Neoplasms / genetics
  • Head and Neck Neoplasms / mortality*
  • Humans
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Invasiveness / pathology
  • Neoplasm Staging
  • Nuclear Proteins / genetics
  • Paclitaxel / administration & dosage*
  • Palliative Care*
  • Polymorphism, Single Nucleotide / genetics*
  • Probability
  • Prognosis
  • Proportional Hazards Models
  • Prospective Studies
  • Survival Analysis
  • Treatment Outcome

Substances

  • Genetic Markers
  • Nuclear Proteins
  • Endonucleases
  • Paclitaxel