Adverse drug events associated with fluorouracil use in patients with metastatic colorectal cancer: a real-world pharmacovigilance study based on the FDA adverse event reporting system

Expert Opin Drug Saf. 2024 Oct;23(10):1295-1307. doi: 10.1080/14740338.2024.2380513. Epub 2024 Jul 23.

Abstract

Background: Fluorouracil (5-FU) is widely used to treat metastatic colorectal cancer (mCRC), but real-world safety data is limited. Our study aimed to evaluate 5-FU's safety profile in a large mCRC population using the FAERS database.

Research design and methods: We conducted disproportionality analyses to identify adverse drug events associated with 5-FU use in mCRC patients from 2004 to 2023. Subgroup analyses, gender difference analyses, and logistic regression were also performed.

Results: We identified 1,458 reports with 5-FU as the primary suspected drug, with males accounting for 48.8% of reports. Gastrointestinal disorders were the most common adverse event (864 cases), while pregnancy-related conditions showed the strongest signal intensity (ROR = 2.97). We found 19 preferred terms with positive signals, including ischemic hepatitis (ROR = 59.32), blood iron increased (ROR = 59.32), and stress cardiomyopathy (ROR = 51.94). Males were more susceptible to weight loss and skin toxicity. Most adverse events occurred within the first month of 5-FU administration.

Conclusion: Our study provides a comprehensive analysis of 5-FU's safety profile in mCRC patients, helping healthcare professionals mitigate risks in clinical practice.

Keywords: FAERS; Fluorouracil; adverse drug events; disproportionality analysis; metastatic colorectal cancer; pharmacovigilance; real-world analysis.

MeSH terms

  • Adult
  • Adverse Drug Reaction Reporting Systems* / statistics & numerical data
  • Aged
  • Aged, 80 and over
  • Antimetabolites, Antineoplastic* / administration & dosage
  • Antimetabolites, Antineoplastic* / adverse effects
  • Colorectal Neoplasms* / drug therapy
  • Colorectal Neoplasms* / pathology
  • Databases, Factual*
  • Female
  • Fluorouracil* / administration & dosage
  • Fluorouracil* / adverse effects
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Metastasis*
  • Pharmacovigilance*
  • Sex Factors
  • United States
  • United States Food and Drug Administration*
  • Young Adult

Substances

  • Fluorouracil
  • Antimetabolites, Antineoplastic