Dihydropyrimidine dehydrogenase level and the redox status in patients with colorectal cancer are prognostic for adverse effects of fluoropyrimidines

Abstract

Drug resistance and toxicity are the most widespread limitations in the pursuit of sufficient antitumor effectiveness and successful control of oncological diseases, including colorectal cancer (CRC). Herein the objective was to investigate some hematological side effects of the chemotherapeutic regimen FOLFOX-4, their relation to dihydropyrimidine dehydrogenase (DPD) levels and the associated alterations in CRC patients’ plasma free-radical scavenging properties and extent of oxidative molecular damage. Thirty-eight patients with histologically confirmed CRC diagnoses, assigned to chemotherapy with the FOLFOX-4 regimen, were recruited. The diagnostic methods included a complete physical examination, blood routine test and general biochemistry. The DPD levels were assayed. The patients’ plasma free-radical scavenging properties and extent of molecular oxidative damage were determined by spectrophotometry and enhanced chemiluminescence. The clinico-pathological and demographics characteristics of the patients were in agreement with the reports from retrospective cohort studies. The FOLFOX-4 regimen induced a decrease in plasma free-radical scavenging properties and increased extent of lipid peroxidation. White blood cells, granulocytes and lymphocytes decreased significantly after the first cycle of the therapy. The patients’ DPD level decreased statistically significantly in the case of severe reduction (more than 25%) of white blood cells and granulocyte counts. The obtained data are in agreement with already known facts concerning the side effects of the FOLFOX-4 regimen and associated changes in redox homeostasis. Genetic predisposition to effectively metabolize and tolerate the applied therapy, i.e. DPD levels, could modulate some aspects of the observed changes in the aforementioned parameters.

Keywords:

• Redox status
• colorectal cancer
• FOLFOX-4
• dihydropyrimidine dehydrogenase

Disclosure statement

No potential conflict of interest was reported by the authors.

Funding

This work was supported by CMS of MU-Sofia under grant D-98/24.06.2020 and the Bulgarian Ministry of Education and Science under the National Program for research ‘Young Scientist and Postdoctoral Students’.

Author statement

All persons meeting the authorship criteria are listed as authors. The authors certify that they have participated sufficiently in the work to take public responsibility for the content. Each author certifies that material or similar material to that presented in this article has not been and will not be published in any other publication.

Data availability

The data that support the findings of this study are available from the corresponding author, N. H-A, upon reasonable request.