Research Progress Of Irinotecans Delaying Diarrhea

Irinotecan is an inhibitor of DNA topoisomerase I

. It is used for first-line treatment on recurrence and worsening of metastatic colorectal cancer after standard chemotherapy regimens. In addition, it also has certain effects on small cell lung cancer, non-small cell lung cancer, breast cancer, gastric cancer, pancreatic cancer and lymphoma. However, delayed diarrhea is the drug toxicity of irinotecan restrictive. Clinical studies show that 20% to 40% of patients who receive the product for treatment have 3 to 4 diarrhea and it causes the early termination of chemotherapy program. Researchers have done extensive research to find a treatment and prevention for irinotecans delaying diarrhea.

Intestinal carboxylesterase, in the intestinal lumen, irinotecan directly into the active metabolite SN-38. Human intestinal biopsy suggests the presence of carboxylesterase, and in vitro tests can be irinotecan into SN-38. Suggesting that inhibition of carboxylesterase in the intestine, reducing the concentration of the active docetaxel metabolite SN-38, may reduce the incidence of delayed diarrhea. Accordingly, the design and synthesis of high affinity intestinal carboxylic acid esterase, acetylcholinesterase and butyrylcholinesterase inhibition of sulfa derivatives carboxylesterase inhibitors. Scientists also study the molecular mechanisms of the selective inhibitor of carboxylesterase to prevent and treat intestinal toxicity of irinotecan. These studies may provide an effective measure for the clinical prevention of delayed diarrhea.

There are clinical antibiotics for the prevention of delayed diarrhea caused by irinotecan. Studies have shown that during treatment with oral neomycin and bacitracin to reduce the incidence of diarrhea, reduce diarrhea extent. Also confirmed the role of the flora in the incidence of adverse reactions. Young flavin can increase the concentration of UGT1A1 in the intestinal cells. The chrysin reduce irinotecan diarrhea caused by mechanisms may be the active metabolite SN-38 a large number converted into inactive SN-38G. Clinical studies also suggest that patients with delayed reduction in the incidence of diarrhea, the utilization rate of imudium reduces. But the research is still need for further randomized clinical validation.

Chinese medicine believes that drug-induced diarrhea is due to all causes stomach the loss of operation of the division, the disorders caused by intestinal conduction. Treatment to Jianpihuashitang for the basic rule. Application to reconcile the reports of gastrointestinal treatment of chemotherapy adverse reactions diarrhea a lot. The available experimental studies have shown that it has to protect the gastrointestinal mucosa, regulate systemic immune function, inhibit COX-2, scavenging reactive oxygen species role, with the role of multi-channel and multi-target.

In short, imudium is a symptomatic medicine to cure the delayed diarrhea. But with the imudium and chia seed dosage increasing, the occurrence possibility of adverse reactions of paralytic ileus increases. From the present findings, we can use antibiotic inhibit bacterial beta-glucuronidase activity and change the metabolic pathway or reduce intestinal active metabolite concentrations. It can prevent and reduce incidences of delaying diarrhea. It may be an alternative to the prevention and reduction of irinotecans delaying diarrhea. But the formers effect still needs further confirmation from large-scale multi-center randomized clinical trial. The latter lacks of clinical random verification and experimental research. With the deepening of irinotecan delayed diarrhea mechanism, an effective prevention and treatment measures will be found for delaying diaeehea.

by: anelwew

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