Can FOLFIRI (Folinic acid, Fluorouracil, Irinotecan) cause cognitive issues?

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Last updated: June 30, 2025View editorial policy

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From the Guidelines

FOLFIRI chemotherapy can cause cognitive issues, but the current evidence does not strongly support a significant association between FOLFIRI and cognitive impairment in the general population of patients with colorectal cancer. The provided evidence focuses on the efficacy and safety of FOLFIRI in older patients, particularly those aged 70 and above, and highlights the importance of considering geriatric characteristics when evaluating treatment outcomes 1. While the study mentions the mini-mental state examination score as a predictive factor for grade 3-4 toxicity, it does not specifically address the incidence of cognitive issues in patients receiving FOLFIRI.

Key points to consider:

  • The evidence suggests that intensive chemotherapy, including FOLFIRI, should be used with caution in patients aged 75 and above with low autonomy and cognitive impairment 1.
  • The addition of bevacizumab to chemotherapy has been shown to improve progression-free survival in older patients, including those aged 75 and above, without significant additional toxicity 1.
  • Cognitive rehabilitation, exercise, adequate sleep, and stress reduction techniques may help mitigate cognitive symptoms in patients experiencing them.
  • It is essential for patients to discuss any cognitive changes with their healthcare provider to determine the best course of management.

In terms of cognitive issues, the evidence is limited, and the most recent and highest-quality study does not provide a clear answer to the question of whether FOLFIRI causes cognitive issues. However, based on the available data, it is reasonable to conclude that while FOLFIRI may contribute to cognitive impairment in some patients, the association is not strongly supported by the current evidence. Patients should be monitored for cognitive changes, and management strategies should be individualized to address any symptoms that arise.

From the FDA Drug Label

5.3 Hyperammonemic Encephalopathy Acute cerebellar syndrome, confusion, disorientation, ataxia, or visual disturbances [see Warnings and Precautions ( 5.4)]

The FDA drug label mentions cognitive issues such as confusion and disorientation as potential adverse reactions to fluorouracil.

  • Key points:
    • Fluorouracil may cause neurotoxicity, including acute cerebellar syndrome and hyperammonemic encephalopathy.
    • The label recommends withholding fluorouracil for patients experiencing acute cerebellar syndrome, confusion, disorientation, ataxia, or visual disturbances.
    • These adverse reactions may indicate a need to reduce the dose or discontinue treatment with fluorouracil 2.

From the Research

FOLFIRI and Cognitive Issues

  • There is no direct evidence in the provided studies that FOLFIRI (Folinic acid, Fluorouracil, Irinotecan) causes cognitive issues 3, 4, 5, 6, 7.
  • The studies primarily focus on the efficacy and toxicity of FOLFIRI in comparison to other chemotherapy regimens for metastatic colorectal cancer.
  • Adverse events such as diarrhea, neutropenia, and neuropathies are reported in the studies, but cognitive issues are not specifically mentioned 3, 4, 7.
  • The lack of information on cognitive issues in these studies suggests that there may not be sufficient research on this specific topic, or it may not be a commonly reported side effect of FOLFIRI.

Related Side Effects

  • The studies do report on various side effects associated with FOLFIRI, including:
    • Diarrhea 3, 4, 7
    • Neutropenia 3, 4, 7
    • Neuropathies 3
    • Alopecia 7
    • Neurosensory toxicity 7
  • These side effects may be related to the chemotherapy agents used in FOLFIRI, but they do not provide direct evidence of cognitive issues.

Limitations

  • The provided studies do not investigate cognitive issues as a primary or secondary endpoint.
  • The studies focus on the efficacy and toxicity of FOLFIRI in the context of metastatic colorectal cancer treatment.
  • Further research may be necessary to determine the potential cognitive effects of FOLFIRI.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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