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.
Keywords: Chemotherapy induced diarrhea, CPT-11 (irinotecan), diarrhea prevention and control, CPT-11 metabolism, toxicity, antidiarrheals/pharmacology, enzyme inhibitors/pharmacology.
Current Drug Targets
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.
Export Options
About this article
Cite this article as:
Swami Umang, Goel Sanjay and Mani Sridhar, Therapeutic Targeting of CPT-11 Induced Diarrhea: A Case for Prophylaxis, Current Drug Targets 2013; 14 (7) . https://dx.doi.org/10.2174/1389450111314070007
DOI https://dx.doi.org/10.2174/1389450111314070007 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
Call for Papers in Thematic Issues
New drug therapy for eye diseases
Eyesight is one of the most critical senses, accounting for over 80% of our perceptions. Our quality of life might be significantly affected by eye disease, including glaucoma, diabetic retinopathy, dry eye, etc. Although the development of microinvasive ocular surgery reduces surgical complications and improves overall outcomes, medication therapy is ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Synthesis and Biological Evaluation of Novel Heterocyclic Imines Linked Coumarin- Thiazole Hybrids as Anticancer Agents
Anti-Cancer Agents in Medicinal Chemistry The Contribution of Nitric Oxide and Carbon Monoxide to Neuronal Function and Development
Central Nervous System Agents in Medicinal Chemistry Photodynamic Therapy using Carbohydrate Conjugated Porphyrins
Drug Design Reviews - Online (Discontinued) (Section A: Molecular, Structural, and Cellular Biology of Drug Transporters) Mammalian Nucleoside Transporters
Current Drug Metabolism Meet Our Editorial Board Member
Current Pharmaceutical Biotechnology Therapeutic Applications of Crocus sativus L. (Saffron): A Review
The Natural Products Journal Molecular Targeted Magnetic Resonance Imaging of Human Colorectal Carcinoma (LoVo) Cells Using Novel Superparamagnetic Iron Oxide- Loaded Nanovesicles: In Vitro and in vivo Studies
Current Cancer Drug Targets Therapeutic Transfer of DNA Encoding Adenoviral E1A
Recent Patents on Anti-Cancer Drug Discovery Antitumor Properties of Natural Compounds and Related Molecules
Recent Patents on Anti-Cancer Drug Discovery Hypersensitivity to Antineoplastic Agents
Current Pharmaceutical Design Radionuclide Molecular Imaging Using Affibody Molecules
Current Pharmaceutical Biotechnology Capillary Electrophoresis–Mass Spectrometry in Metabolomics: The Potential for Driving Drug Discovery and Development
Current Drug Metabolism Curcumin in Combined Cancer Therapy
Current Pharmaceutical Design Docking Studies for Multi-Target Drugs
Current Drug Targets SRC: Regulation, Role in Human Carcinogenesis and Pharmacological Inhibitors
Current Pharmaceutical Design Immunomodulatory Activity of Garlic
Current Immunology Reviews (Discontinued) Pharmacogenetics of Childhood Acute Lymphoblastic Leukemia
Current Pharmacogenomics Development of NGR-Based Anti-Cancer Agents for Targeted Therapeutics and Imaging
Anti-Cancer Agents in Medicinal Chemistry Epigenetic Interventions Increase the Radiation Sensitivity of Cancer Cells
Current Pharmaceutical Design Targeting Inflammation in Cancer-Related-Fatigue: A Rationale for Mistletoe Therapy as Supportive Care in Colorectal Cancer Patients
Inflammation & Allergy - Drug Targets (Discontinued)