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Enterotoxicity of chemotherapeutic agents

Smitha S Krishnamurthi, MD
Section Editor
Reed E Drews, MD
Deputy Editor
Diane MF Savarese, MD


Gastrointestinal (GI) toxicity due to chemotherapeutic drugs is a common problem in cancer patients. The specific chemotherapy-related GI complications that are reviewed here include diarrhea, constipation, colitis (neutropenic, C. difficile-induced, and immune-mediated), and intestinal perforation. Chemotherapy-induced oral toxicity (mucositis), and nausea and vomiting are discussed separately. (See "Oral toxicity associated with chemotherapy" and "Pathophysiology and prediction of chemotherapy-induced nausea and vomiting" and "Prevention and treatment of chemotherapy-induced nausea and vomiting in adults".)


Chemotherapy-induced diarrhea (CID) is most commonly described with fluoropyrimidines (particularly fluorouracil [FU] and capecitabine) and irinotecan. Diarrhea is the dose-limiting and major toxicity of regimens containing a fluoropyrimidine with or without irinotecan.

Pathogenesis — Both FU and irinotecan cause acute damage to the intestinal mucosa, leading to loss of epithelium [1,2]. FU induces mitotic arrest of crypt cells, leading to an increase in the ratio of immature secretory crypt cells to mature villous enterocytes [1,3]. The increased volume of fluid that leaves the small bowel exceeds the absorptive capacity of the colon, leading to clinically significant diarrhea.

With irinotecan, early onset diarrhea occurs during or within several hours of drug infusion in 45 to 50 percent of patients and is cholinergically mediated [4]. This effect is thought to be due to structural similarity of the drug with acetylcholine. In contrast, late irinotecan-associated diarrhea is not cholinergically mediated. The pathophysiology of late diarrhea appears to be multifactorial with contributions from dysmotility and secretory factors as well as a direct toxic effect on the intestinal mucosa [5,6].

Irinotecan produces mucosal changes associated with apoptosis, such as epithelial vacuolization, and goblet cell hyperplasia, suggestive of mucin hypersecretion [2]. These changes appear related to the accumulation of the active metabolite of irinotecan, SN-38, in the intestinal mucosa [7].


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