Title:Therapeutic Targeting of CPT-11 Induced Diarrhea: A Case for Prophylaxis
Volume: 14
Issue: 7
Author(s): Umang Swami, Sanjay Goel and Sridhar Mani
Affiliation:
Keywords:
Chemotherapy induced diarrhea, CPT-11 (irinotecan), diarrhea prevention and control, CPT-11 metabolism, toxicity,
antidiarrheals/pharmacology, enzyme inhibitors/pharmacology.
Abstract: CPT-11 (irinotecan), a DNA topoisomerase I inhibitor is one of the main treatments for colorectal cancer. The
main dose limiting toxicities are neutropenia and late onset diarrhea. Though neutropenia is manageable, CPT-11 induced
diarrhea is frequently severe, resulting in hospitalizations, dose reductions or omissions leading to ineffective treatment
administration. Many potential agents have been tested in preclinical and clinical studies to prevent or ameliorate CPT-11
induced late onset diarrhea. It is predicted that prophylaxis of CPT-11 induced diarrhea will reduce sub-therapeutic dosing
as well as hospitalizations and will eventually lead to dose escalations resulting in better response rates. This article reviews
various experimental agents and strategies employed to prevent this debilitating toxicity. Covered topics include
schedule/dose modification, intestinal alkalization, structural/chemical modification, genetic testing, anti-diarrheal therapies,
transporter (ABCB1, ABCC2, BCRP2) inhibitors, enzyme (β-glucuronidase, UGT1A1, CYP3A4, carboxylesterase,
COX-2) inducers and inhibitors, probiotics, antibiotics, adsorbing agents, cytokine and growth factor activators and inhibitors
and other miscellaneous agents.
