A Comprehensive Review on Irinotecan-Induced Delayed Diarrhea: From Mechanisms to Therapeutic Options

Irinotecan is a first-line medication for metastatic colorectal cancer. It is known that irinotecan-induced delayed diarrhea is closely related to metabolic processes in the human body. In particular, the synergies of multiple metabolic enzymes/transporters mediate the transport/regeneration of intestinal SN38. This efficient metabolite derived from irinotecan not only exerts robust cytotoxic effects, but also extends contact duration with the intestinal wall during enterohepatic circulation. These factors further affect the intestinal microenvironment, including intestinal flora disorder, intestinal immune dysregulation, and intestinal barrier impairment, which ultimately causes the occurrence of delayed diarrhea. At present, dose adjustment of irinotecan and combining drugs are common measures for clinical use. However, these regimens have shown limited therapeutic efficacy and face the risk of chemotherapy failure. Numerous studies have shown that herbal medicines and derived phytochemicals may also be promising complementary treatments. The characteristics of multi-target regulation of herbs are very suitable for the intervention strategy of complex diseases with multiple pathogenic links. This review focuses on the development of irinotecan-induced delayed diarrhea. We generalized the complex pathogenesis in detail and summarized relevant potential drugs and clinical agents. Special attention was paid to the feasibility of traditional Chinese medicine treatment. This will help expand medication regimens for irinotecan-related diarrhea and provide a reference for the development of precision drugs.