Can FOLFOX (oxaliplatin, leucovorin, and fluorouracil) cause seizures or cardiotoxicity?

FOLFOX and Risk of Seizures and Cardiotoxicity

FOLFOX chemotherapy can cause both seizures and cardiotoxicity, though seizures are rare and cardiotoxicity occurs in approximately 3% of patients. The management of these side effects requires careful monitoring and prompt intervention.

Seizure Risk with FOLFOX

Seizures are a rare but documented adverse effect of FOLFOX therapy, particularly related to the oxaliplatin component:

• Oxaliplatin can cause tonic-clonic seizures even in the absence of posterior reversible leukoencephalopathy syndrome (PRES) 1
• Seizures typically occur during or shortly after administration
• Neurologic toxicity from oxaliplatin is more commonly manifested as peripheral neuropathy, but can include more serious central nervous system effects

Cardiotoxicity Risk with FOLFOX

Cardiotoxicity is primarily associated with the fluorouracil (5-FU) component of FOLFOX:

• The FDA label for fluorouracil specifically warns about cardiotoxicity, including angina, myocardial infarction/ischemia, arrhythmia, and heart failure 2

• Risk factors for cardiotoxicity include:

  • Administration by continuous infusion rather than IV bolus
  • Pre-existing coronary artery disease
  • Combination with leucovorin (as in FOLFOX)

• The overall risk of cardiotoxicity with 5-FU/leucovorin is approximately 3% 3

• Patients with a history of cardiac disease have a significantly higher risk (15.1%) compared to those without cardiac history (1.5%) 3

Monitoring and Management

For Seizures:

1. Monitor for neurological symptoms during and after FOLFOX administration
2. If seizures occur:
   • Immediately discontinue oxaliplatin
   • Consider switching to an alternative regimen like FOLFIRI (replacing oxaliplatin with irinotecan) 1
   • Perform neurological evaluation including EEG and brain MRI to rule out other causes

For Cardiotoxicity:

1. Screen patients for pre-existing cardiac disease before initiating FOLFOX
2. Monitor for cardiac symptoms (chest pain, arrhythmias, heart failure)
3. If cardiotoxicity develops:
   • Withhold fluorouracil 2
   • Evaluate cardiac status
   • Consider alternative regimens if treatment must continue

Special Considerations

• Neurological symptoms typically appear within 3 days of treatment 3
• Peripheral neuropathy is the most common neurological adverse effect of oxaliplatin, affecting up to 68% of patients receiving FOLFOX 4
• Discontinuation of oxaliplatin should be considered after 3 months of therapy or sooner if unacceptable neurotoxicity develops 5
• Cardiotoxicity symptoms typically develop within 2-6 days of treatment initiation 3

Alternative Regimens

If FOLFOX causes severe neurological or cardiac toxicity, alternative regimens to consider include:

1. FOLFIRI (replacing oxaliplatin with irinotecan) 5, 1
2. Capecitabine-based regimens (with appropriate dose adjustments) 5
3. 5-FU/LV without oxaliplatin for patients with severe neurotoxicity 5

In conclusion, while both seizures and cardiotoxicity can occur with FOLFOX therapy, they require different monitoring approaches and management strategies based on which component of the regimen is likely causing the adverse effect.