Cyclooxygenase-2 inhibition with celecoxib enhances antitumor efficacy and reduces diarrhea side effect of CPT-11.

Abstract

Combining anticancer drugs with different mechanisms of action has the potential to enhance antitumor effect. CPT-11 (Camptosar, irinotecan), a topoisomerase I inhibitor, has been shown to be highly effective in the treatment of a variety of cancers. However, its clinical usage is often complicated by late diarrhea. A number of studies have shown that cyclooxygenase (COX)-2 is overexpressed in many forms of human tumors, suggesting that COX-2 inhibition may be useful in the treatment of cancer. In this study, we used two mouse tumor models (HT-29 and colon-26 cells) to evaluate the effect of combining CPT-11 with celecoxib on tumor growth. We also assessed the involvement of COX-2 in the pathogenesis of CPT-11-induced late diarrhea using a rat model. Results indicate that celecoxib enhances the antitumor effect of CPT-11 and reduces the severity of late diarrhea in a dose-dependent manner. The extended benefits of combining celecoxib with CPT-11 may significantly improve the outcome of cancer patients.

• Authors: Ovidiu C Trifan, William F Durham, Valerie S Salazar, Jennifer Horton, Benjamin D Levine, Ben S Zweifel, Thomas W Davis, Jaime L Masferrer
• Journal: Cancer research (Cancer Res) Vol. 62 Issue 20 Pg. 5778-84 (Oct 15 2002) ISSN: 0008-5472 [Print] United States
• PMID: 12384538 (Publication Type: Journal Article)

Chemical References

• Cyclooxygenase 2 Inhibitors
• Cyclooxygenase Inhibitors
• Isoenzymes
• Membrane Proteins
• Pyrazoles
• Sulfonamides
• Irinotecan
• Cyclooxygenase 2
• PTGS2 protein, human
• Prostaglandin-Endoperoxide Synthases
• Celecoxib
• Dinoprostone
• Camptothecin

Topics

• Animals
• Antineoplastic Combined Chemotherapy Protocols (pharmacology)
• Camptothecin (administration & dosage, adverse effects, analogs & derivatives, pharmacology)
• Celecoxib
• Colon (metabolism)
• Cyclooxygenase 2
• Cyclooxygenase 2 Inhibitors
• Cyclooxygenase Inhibitors (pharmacology)
• Diarrhea (chemically induced, prevention & control)
• Dinoprostone (biosynthesis, physiology)
• Drug Administration Schedule
• Drug Synergism
• HT29 Cells (drug effects)
• Humans
• Irinotecan
• Isoenzymes (antagonists & inhibitors)
• Male
• Membrane Proteins
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Prostaglandin-Endoperoxide Synthases
• Pyrazoles
• Rats
• Rats, Sprague-Dawley
• Sulfonamides (administration & dosage, pharmacology)
• Weight Loss (drug effects)
• Xenograft Model Antitumor Assays