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Clinical Cancer Research Vol. 7, 1136-1141, May 2001
© 2001 American Association for Cancer Research

Advances in Brief

Modulation of Irinotecan-induced Diarrhea by Cotreatment with Neomycin in Cancer Patients1

Diederik F. S. Kehrer2, Alex Sparreboom, Jaap Verweij, Peter de Bruijn, Corine A. Nierop, Jacqueline van de Schraaf, Elisabeth J. Ruijgrok and Maja J. A. de Jonge

Department of Medical Oncology, Rotterdam Cancer Institute (Daniel den Hoed Kliniek) and University Hospital Rotterdam, 3075 EA Rotterdam [D. F. S. K., A. S., J. V., P. d. B., C. A. N., J. v. d. S., M. J. A. d. J], and Department of Pharmacy, University Hospital Rotterdam, 3015 GD Rotterdam [E. J. R.], the Netherlands

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 >=2 after receiving CPT-11 alone (350 mg/m2 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 >= 0.22). However, it changed fecal ß-glucuronidase activity from 7.03 ± 1.76 µg/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 ß-glucuronidase plays a crucial role in CPT-11-induced diarrhea without affecting enterocycling and systemic SN-38 levels.




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Copyright © 2001 by the American Association for Cancer Research.