Modulation of irinotecan-induced diarrhea by cotreatment with neomycin in cancer patients
This study was designed to evaluate irinotecan (CPT-11) disposition and pharmacodynamics in the presence and absence of the broad-spectrum antibiotic neomycin. Seven evaluable cancer patients experiencing diarrhea graded > or =2 after receiving CPT-11 alone (350 mg/m(2) i.v. once every 3 weeks) received the same dose combined with oral neomycin at 1000 mg three times per day (days -2 to 5) in the second course. Neomycin had no effect on the systemic exposure of CPT-11 and its major metabolites (P > or = 0.22). However, it changed fecal beta-glucuronidase activity from 7.03 +/- 1.76 microg/h/mg (phenolphthalein assay) to undetectable levels and decreased fecal concentrations of the pharmacologically active metabolite SN-38. Although neomycin had no significant effect on hematological toxicity (P > 0.05), diarrhea ameliorated in six of seven patients (P = 0.033). Our findings indicate that bacterial beta-glucuronidase plays a crucial role in CPT-11-induced diarrhea without affecting enterocycling and systemic SN-38 levels.
|, , , , , , , , , , , ,|
|Clinical Cancer Research|
|Organisation||Erasmus MC: University Medical Center Rotterdam|
Kehrer, D.F.S, Sparreboom, A, Verweij, J, de Bruijn, P.J, Nierop, C.A, van de Schraaf, J, … de Jonge, M.J.A. (2001). Modulation of irinotecan-induced diarrhea by cotreatment with neomycin in cancer patients. Clinical Cancer Research. Retrieved from http://hdl.handle.net/1765/9635