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.
|Keywords||Adolescent, Adult, Aged, Anti-Bacterial Agents/therapeutic use, Antineoplastic Agents, Phytogenic/*adverse effects, Camptothecin/*adverse effects/analogs & derivatives, Cross-Over Studies, Diarrhea/chemically induced/*drug therapy, Humans, Middle aged, Neomycin/*therapeutic use, Neoplasms/*complications/drug therapy, Research Support, Non-U.S. Gov't|
Kehrer, D.F.S., Sparreboom, A., Verweij, J., de Bruijn, P., 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