Substantial activity of budesonide in patients with irinotecan (CPT-11) and 5-fluorouracil induced diarrhea and failure of loperamide treatment.

BACKGROUND Diarrhea is one of the most disturbing effects of chemotherapy, affecting quality of life on the one hand and limiting applicable doses on the other. Irinotecan (CPT-11) and 5-fluorouracil (5-FU) are associated with an elevated risk of developing severe diarrhea. Standard therapy consists of high-dose loperamide, but is associated with frequent failure. Other therapeutic regimens are still experimental. Endoscopic examination of a patient with severe loperamide-resistant diarrhea after CPT-11 chemotherapy revealed an inflammation of the ileo-coecal region. Oral therapy with the topical corticosteroid budesonide was immediately effective. This led to a phase I study of budesonide in CPT-11- and 5-FU-induced and loperamide-refractory diarrhea. PATIENTS AND METHODS Fourteen patients with CPT-11- and seven patients with 5-FU-induced grade 3-4 (NCI/WHO) diarrhea and loperamide failure were enrolled in this study. All patients had metastatic colorectal cancer. RESULTS In 86% of the CPT-11- and 57% of the 5-FU-treated patients with grade 3-4 diarrhea and loperamide failure, treatment with budesonide resulted in a reduction of diarrhea severity by at least two grades. CONCLUSIONS The orally administered topical active steroid budesonide is highly effective in the therapy of loperamide-refractory chemotherapy (CPT-11 or 5-FU)-induced diarrhea.