Journal
CURRENT DRUG TARGETS
Volume 14, Issue 7, Pages 777-797Publisher
BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/1389450111314070007
Keywords
Chemotherapy induced diarrhea; CPT-11 (irinotecan); diarrhea prevention and control; CPT-11 metabolism; toxicity; antidiarrheals/pharmacology; enzyme inhibitors/pharmacology
Categories
Funding
- NIH [CA 127231]
- Damon Runyon Clinical Investigator Award
Ask authors/readers for more resources
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 (beta-glucuronidase, UGT1A1, CYP3A4, carboxylesterase, COX-2) inducers and inhibitors, probiotics, antibiotics, adsorbing agents, cytokine and growth factor activators and inhibitors and other miscellaneous agents.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available