Genetic Markers Predict Response and Toxicity to FOLFOX Chemotherapy in Metastatic Colorectal Cancer

Strategic Insights -

Researchers from the Repatriation General Hospital in Sydney, Australia, have investigated the potential of genetic markers to predict response and toxicity to FOLFOX chemotherapy in metastatic colorectal cancer (mCRC) patients. The study analyzed tumor tissues from 118 mCRC patients who underwent FOLFOX treatment and found that specific genetic alterations and polymorphisms could be correlated with clinical outcomes. The results suggest that individual genetic variation may be used to personalize chemotherapy treatment and optimize clinical outcomes.

Key Takeaways:

  • The study investigated three genetic alterations (TP53 mutation, Kras mutation, and microsatellite instability) and three polymorphisms (MTHFR C677T, ERCC1-118, and XRCC1-399) for their ability to predict response, survival, and toxicity to FOLFOX chemotherapy in mCRC patients.
  • Genotyping for common single nucleotide polymorphisms in the MTHFR, ERCC1, and XRCC1 genes was carried out using PCR techniques, and these genetic markers were correlated with clinical response, survival, and toxicity to treatment.
  • Patients with the T allele of ERCC1-118 showed significantly worse progression-free survival in univariate analysis (HR=2.62; 95% CI=1.14-6.02; p=0.02).
  • None of the genetic alterations or polymorphisms showed significant association with clinical response to FOLFOX, but the MTHFR, ERCC1, and XRCC1 polymorphisms showed no associations with overall haematological, gastrointestinal, or neurological toxicity to FOLFOX.
  • The ERCC1-118 and MTHFR C677T polymorphisms were associated with progression and severe diarrhea, respectively, after FOLFOX treatment in mCRC patients.

Statistics:

  • 118 mCRC patients were included in the study.
  • 45% of patients had the T allele of ERCC1-118.
  • 26% of MTHFR 677 TT genotype patients developed grade 3 or 4 diarrhea compared to 6% of CC or CT genotype patients (p=0.02).
  • The study found that individual genetic variation may allow personalized selection of chemotherapy to optimize clinical outcomes.

Sources:

  • W. Chua et al. (2009). "Molecular markers of response and toxicity to FOLFOX chemotherapy in metastatic colorectal cancer." British Journal of Cancer, 101(6), 998-1004.