What is the role of budesonide in patients (pts) undergoing chemotherapy?

Budesonide in Patients on Chemotherapy

Budesonide 3 mg three times daily added to loperamide is effective for treating loperamide-refractory chemotherapy-induced diarrhea, particularly from irinotecan and 5-fluorouracil, but has no role as prophylaxis. 1

Treatment of Established Chemotherapy-Induced Diarrhea

Irinotecan-Associated Diarrhea

• For late-onset irinotecan diarrhea that fails loperamide, add budesonide 3 mg orally three times daily until symptom resolution (Strength of Recommendation: B, Quality of Evidence: II). 1
• In a phase I study of 14 patients with CPT-11-induced grade 3-4 diarrhea refractory to loperamide, budesonide reduced diarrhea severity by at least two grades in 86% of patients. 2
• Stop budesonide if no response occurs after 72 hours. 1

5-Fluorouracil-Associated Diarrhea

• Budesonide combined with loperamide showed effectiveness in 57% of patients with 5-FU-induced grade 3-4 diarrhea who failed loperamide monotherapy. 2
• The same dosing regimen applies: 3 mg three times daily until resolution. 1

Mechanism of Benefit

• Endoscopic examination in patients with severe chemotherapy-induced diarrhea has revealed inflammation of the ileocecal region, explaining budesonide's efficacy as a topically active corticosteroid. 2
• Budesonide has high topical anti-inflammatory activity with minimal systemic absorption due to extensive first-pass metabolism. 3, 4

Prophylactic Use: Not Recommended

Prophylactic budesonide for preventing chemotherapy-induced diarrhea is not recommended. 1

• A randomized controlled trial showed no therapeutic benefit to prophylactic budesonide for preventing irinotecan-induced enterocolitis (Strength of Recommendation: C, Quality of Evidence: II). 1
• Neomycin 500 mg twice daily was evaluated only as secondary prophylaxis in patients who experienced grade II-IV diarrhea during the first chemotherapy cycle, not as primary prevention. 1

Special Context: Immune Checkpoint Inhibitor Colitis

For patients on immunotherapy (a distinct form of cancer treatment):

• Budesonide has a specific role only in ICI-associated microscopic colitis (histologic lymphocytic inflammation without macroscopic signs or small bowel involvement). 1
• Patients with ICI-associated microscopic colitis were highly responsive to colonic budesonide and many could continue immunotherapy while on concurrent budesonide treatment. 1
• However, prophylactic budesonide showed no benefit for preventing ipilimumab-induced enterocolitis in a randomized controlled trial. 1

Important Caveats

When to Avoid Budesonide

• Always exclude infectious diarrhea before initiating budesonide, particularly in neutropenic patients where antimotility agents and immunosuppression carry increased risk of bacteremia. 1, 5
• Budesonide should only be used after loperamide failure, not as first-line therapy. 1

Neutropenic Patients

• Exercise careful risk-benefit assessment in neutropenic patients, as overdosage of any antimotility agent may lead to iatrogenic ileus with increased bacteremia risk. 1
• In long-term neutropenic patients, this complication risk is particularly elevated. 1

Alternative Second-Line Options

If budesonide is contraindicated or ineffective:

• Octreotide 500 μg subcutaneously three times daily is an alternative second-line agent (Strength of Recommendation: B, Quality of Evidence: II). 1, 5
• Acetorphan 100 mg three times daily for 48 hours is another option. 1
• Psyllium seeds may be considered for persistent severe diarrhea. 1

Hospitalization Criteria

• Patients with severe diarrhea persisting >48 hours despite antimotility agents should be hospitalized for intravenous fluid replacement. 1, 5