Eflornithine for chemoprevention in the high-risk population of colorectal cancer: a systematic review and meta-analysis with trial sequential analysis

Lifeng Yang; Yan Wang; Shasha Hu; Xiaoyan Wang

doi:10.3389/fonc.2023.1281844

Eflornithine for chemoprevention in the high-risk population of colorectal cancer: a systematic review and meta-analysis with trial sequential analysis

Front Oncol. 2023 Nov 15:13:1281844. doi: 10.3389/fonc.2023.1281844. eCollection 2023.

Authors

Lifeng Yang¹, Yan Wang², Shasha Hu³, Xiaoyan Wang¹

Affiliations

¹ School of Nursing, Hexi University, Zhangye, China.
² Peking University First Hospital Ningxia Women and Children's Hospital (Ningxia Hui Autonomous Region Maternal and Child Health Hospital), Nursing Department, Yinchuan, Ningxia Hui Autonomous Region, China.
³ The First Ward of the Department of Gynecology, The First Hospital of Lanzhou University, Lanzhou, China.

Abstract

Objectives: To evaluate the efficacy of Difluoromethylornithine (DFMO) chemoprevention in the high-risk population for colorectal cancer (CRC).

Methods: Meta-analysis was conducted to assess the caliber of the included literature by searching five databases for randomized controlled trials of DFMO chemoprevention in the high-risk population of CRC, with RevMan 5.4, Stata 15.0 and TSA 0.9.5.10 employed to statistically analyze the extracted data. Grade profiler 3.6 was employed for grading the evidence for the outcome indicators (disease progression and adenoma incidence).

Results: Six trials were finally included in this research, with the collective data indicating that the DFMO combination therapy was efficacious in lowering the incidence of recurrent adenomas in patients who had experienced advanced CRC [RR 0.34, 95% CI 0.14 - 0.83, P < 0.05]. Meta-analysis showed that DFMO combined therapy had no statistical difference in disease progression in patients with familial adenomatous polyposis[RR 0.52, 95% CI 0.14 - 1.86, P > 0.05]; Trial Sequential Analysis reveals that the combination therapy of DFMO effectively diminishes the occurrence of recurrent adenomas in patients with a history of advanced colorectal tumors, displaying a Risk Ratio (RR) of 0.33 with a 95% Confidence Interval (CI) of 0.12 - 0.90 and a significance level of P < 0.05. This combination exhibits a statistically significant difference. Subgroup analysis demonstrates that, depending on the drug treatment regimen (DFMO+ Aspirin/DFMO+ Sulindac), the combination of DFMO and aspirin exhibits an effect comparable to a placebo in diminishing the occurrence of new adenomas in patients with a history of advanced colorectal tumors. However, the combination of DFMO and sulindac significantly mitigates the incidence of recurrent adenomas in this patient population.

Conclusion: This meta-analysis indicates that the existing randomized controlled trials are adequate to ascertain the efficacy of DFMO combination therapy in diminishing the incidence of recurrent adenomas in patients who have previously encountered advanced colorectal tumors. However, further clinical trials need to be conducted to evaluate the optimum dosage and treatment course of prophylactic implementation of DFMO combination therapy in high-risk populations.

Keywords: Eflornithine; chemoprevention; colorectal cancer; high-risk group; meta-analysis; trial sequential analysis.

Publication types

Systematic Review

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This study was funded by the First Hospital of Lanzhou University (No.2007002002302), The President’s Youth Fund of Hexi University (No.QN2022011), Hexi University Curriculum Ideological and Political Teaching Research Project (HXXYJY-2021-24) and the Innovation Fund project of Gansu Provincial Department of Education (No.2022B-192) are supported.