What chemotherapy regimens for colorectal cancer (CRC) are associated with behavioral changes?

Chemotherapy Regimens for Colorectal Cancer Associated with Behavioral Changes

Irinotecan-containing regimens (FOLFIRI) are most associated with behavioral changes in colorectal cancer patients and should be used with caution in patients at risk for neuropsychiatric effects. 1

Common Chemotherapy Regimens for Colorectal Cancer

The standard chemotherapy regimens for colorectal cancer include:

1. FOLFOX regimens: 5-FU/leucovorin/oxaliplatin

   • mFOLFOX6: Oxaliplatin 85 mg/m² IV over 2 hours on day 1, leucovorin 400 mg/m² IV over 2 hours on day 1,5-FU 400 mg/m² IV bolus on day 1, followed by 1,200 mg/m²/day continuous infusion for 2 days 2
   • CAPOX (XELOX): Oxaliplatin 130 mg/m² IV on day 1 and capecitabine 1,000 mg/m² twice daily for 14 days, every 3 weeks 2

2. FOLFIRI regimens: 5-FU/leucovorin/irinotecan

   • Irinotecan 180 mg/m² IV over 90 minutes on day 1, leucovorin 400 mg/m² IV over 2 hours on day 1,5-FU 400 mg/m² IV bolus on day 1, followed by 1,200 mg/m²/day continuous infusion for 2 days 2

Behavioral Changes Associated with Chemotherapy

Irinotecan-Related Behavioral Changes

Irinotecan is most commonly associated with neuropsychiatric effects, including:

• Acute cholinergic syndrome that can manifest as behavioral changes
• Confusion and altered mental status, particularly when combined with severe diarrhea leading to electrolyte imbalances
• Behavioral changes secondary to volume depletion and renal impairment 1

The FDA label for irinotecan specifically warns about cholinergic reactions that can affect mental status and behavior, particularly during or shortly after infusion 1.

Oxaliplatin-Related Behavioral Changes

Oxaliplatin primarily causes peripheral neuropathy but can occasionally lead to:

• Anxiety
• Depression
• Sleep disturbances
• Cognitive changes 3, 4

These effects are generally less pronounced than with irinotecan but should be monitored.

Management Algorithm for Patients at Risk for Behavioral Changes

1. Risk Assessment:

   • Evaluate baseline cognitive function
   • Check for history of psychiatric disorders
   • Review medications that might interact with chemotherapy
   • Assess renal function and electrolyte status

2. Regimen Selection:

   • For patients at high risk of behavioral changes: Consider FOLFOX or fluoropyrimidine monotherapy
   • For patients with low risk: Any standard regimen (FOLFOX, FOLFIRI) based on disease characteristics

3. Preventive Measures:

   • For irinotecan-containing regimens: Prophylactic atropine (0.25-1 mg IV/SC) to prevent cholinergic symptoms 1
   • Aggressive hydration and electrolyte management
   • Early intervention for diarrhea with loperamide

4. Monitoring:

   • Regular assessment of cognitive function and behavior
   • Electrolyte monitoring, especially during episodes of diarrhea
   • Family/caregiver education about potential behavioral changes

5. Management of Behavioral Changes:

   • Dose reduction or interruption if severe behavioral changes occur
   • Consider switching from FOLFIRI to FOLFOX if behavioral changes are significant
   • Psychiatric consultation for persistent symptoms

Important Considerations and Caveats

• Electrolyte Imbalances: Severe diarrhea from irinotecan can lead to electrolyte abnormalities that manifest as behavioral changes 1
• Dehydration: Volume depletion can cause acute mental status changes, especially in elderly patients
• Drug Interactions: Assess for medications that might potentiate neuropsychiatric effects
• UGT1A1 Testing: Consider testing for UGT1A1*28 genotype before irinotecan therapy, as patients with certain genotypes may be at higher risk for severe toxicity 1

Pitfalls to Avoid

• Overlooking early signs: Subtle behavioral changes may precede more severe manifestations
• Attributing all symptoms to disease progression: Behavioral changes are often drug-related and potentially reversible
• Continuing full-dose therapy: Dose reduction or temporary interruption may be necessary when behavioral changes occur
• Inadequate management of diarrhea: Aggressive treatment of diarrhea can prevent electrolyte disturbances that lead to behavioral changes

By carefully selecting chemotherapy regimens and implementing preventive strategies, the risk of behavioral changes in colorectal cancer patients can be minimized while maintaining effective treatment.