Neomycin as secondary prophylaxis for irinotecan-induced diarrhea

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Abstract
Irinotecan-based chemotherapy is widely used for colorectal cancer (CRC) and small-cell lung cancer (SCLC). Irinotecan-associated diarrhea can be dose limiting and sometimes necessitates termination of chemotherapy. Loperamide at high doses can ameliorate irinotecan-associated diarrhea, but in large trials the rate of grade III/IV diarrhea remains 16–22% [1, 2]. Irinotecan is hydrolyzed in vivo to form SN38, the active metabolite. SN38 is inactivated by UDP-glucuronyltranferase to form SN38-G, which is excreted biliarily [3]. Intestinal bacterial β-glucuronidases can deglucuronate SN38-G into active SN38, which causes mucosal damage in the small intestine resulting in toxic diarrhea. An earlier study demonstrated that oral neomycin (3 × 1000 mg daily) effectively inhibits fecal β-glucuronidase activity, resulting in a reduction of diarrhea in patients treated with irinotecan 350 mg/m2, without affecting systemic SN38 levels [4].