Therapeutic targeting of CPT-11 induced diarrhea

a case for prophylaxis.

Research output: Contribution to journalArticle

34 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)777-797
Number of pages21
JournalCurrent Drug Targets
Volume14
Issue number7
StatePublished - Jun 2013
Externally publishedYes

Fingerprint

irinotecan
Diarrhea
Neutropenia
Toxicity
Hospitalization
Topoisomerase I Inhibitors
Therapeutics
Cytochrome P-450 CYP3A
Growth Inhibitors
Carboxylesterase
Cyclooxygenase 2 Inhibitors
Glucuronidase
Chemical modification
Probiotics
Genetic Testing
Enzyme Inhibitors
Colorectal Neoplasms
Intercellular Signaling Peptides and Proteins
Appointments and Schedules
Cytokines

ASJC Scopus subject areas

  • Drug Discovery
  • Pharmacology
  • Clinical Biochemistry
  • Molecular Medicine

Cite this

Therapeutic targeting of CPT-11 induced diarrhea : a case for prophylaxis. / Swami, Umang; Goel, Sanjay; Mani, Sridhar.

In: Current Drug Targets, Vol. 14, No. 7, 06.2013, p. 777-797.

Research output: Contribution to journalArticle

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