Nucleic Acid Metabolizing Enzyme Levels Predict Chemotherapy Effects in Advanced and Recurrent Colorectal Cancer

Asian Pac J Cancer Prev. 2022 Mar 1;23(3):1005-1011. doi: 10.31557/APJCP.2022.23.3.1005.

Abstract

Background: Thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) predict the effects of fluoropyrimidine. However, the effects of FOLFOX therapy from the perspective of fluorouracil plus leucovorin (FL) remain underexplored. Hence, the relationship between mFOLFOX6 therapy (mFOLFOX6) and therapeutic efficacy was evaluated in patients with advanced/recurrent colorectal cancer (CRC).

Methods: Correlations between TS and DPD and primary and metastatic lesions in recurrent CRC were analyzed. Univariate and multivariate analyses of TS and DPD in combination with response rate (RR), progression-free survival (PFS), and overall survival (OS) were performed.

Results: A positive correlation between DPD and primary and metastatic lesions; correlations between TS and RR, DPD and RR, and PFS and OS; and significant differences for RR and DPD and TS, PFS and DPD, and OS and DPD were obtained.

Conclusion: Nucleic acid metabolizing enzymes in primary lesions can be used to predict mFOLFOX6 efficacy in patients with recurrent CRC.

Keywords: Recurrent and advanced colorectal cancer; dihydropyrimidine dehydrogenase (DPD); mFOLFOX6 therapy; thymidylate synthase (TS).

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols* / therapeutic use
  • Colorectal Neoplasms* / pathology
  • Dihydrouracil Dehydrogenase (NADP) / metabolism*
  • Fluorouracil / therapeutic use
  • Humans
  • Leucovorin / therapeutic use
  • Neoplasm Recurrence, Local* / drug therapy
  • Organoplatinum Compounds / therapeutic use
  • RNA, Messenger
  • Thymidylate Synthase / metabolism*

Substances

  • Organoplatinum Compounds
  • RNA, Messenger
  • Dihydrouracil Dehydrogenase (NADP)
  • Thymidylate Synthase
  • Leucovorin
  • Fluorouracil

Supplementary concepts

  • Folfox protocol