Intratumoral COX-2 gene expression is a predictive factor for colorectal cancer response to fluoropyrimidine-based chemotherapy.

Abstract

PURPOSE:

Cyclooxygenase-2 (COX-2) is generally elevated in tumors compared with normal tissue and apparently has an important role in tumor development. A number of studies have found high expression of COX-2 to be an unfavorable prognostic factor for overall survival in several cancers. However, the influence of COX-2 expression levels on tumor response to chemotherapy has been relatively little studied. The purpose of this study was to ascertain if COX-2 gene expression is associated with tumor response in the clinical treatment of colorectal cancer with the fluoropyrimidine-based therapy S-1.

EXPERIMENTAL DESIGN:

Patients with advanced (stage IV) colorectal cancer were treated with S-1 twice daily based on the patient's body surface area (BSA; BSA < 1.25 m2, 80 mg/d; 1.25 m2 < or = BSA < 1.5 m2, 100 mg/d; BSA > or = 1.5 m2, 120 mg/d) for 28 days followed by a 2-week period rest. mRNA was isolated from paraffin-embedded pretreatment primary tumor specimens and expression levels of COX-2 relative to beta-actin as the internal reference gene were measured using a quantitative reverse transcription-PCR (Taqman) system.

RESULTS:

The overall response rate in a group of 44 patients treated with S-1 was 40.9%. Sufficient tumor tissue was available from 40 of these patients for COX-2 mRNA quantitation. COX-2 gene expression was significantly lower in the responding tumors compared with the nonresponders (P = 0.012, Wilcoxon test). Patients with COX-2 values above the cutoff value of 3.28 x 10(-3) had a significantly shorter survival than those with COX-2 gene expressions below the cutoff value (adjusted P = 0.031).

CONCLUSIONS:

Intratumoral COX-2 gene expression is associated with likelihood of response to chemotherapy with S-1 and is a prognostic factor for survival of patients after the start of S-1 chemotherapy.

• Authors: Kazumi Uchida, Sylke Schneider, Ji Min Yochim, Hidekazu Kuramochi, Kazuhiko Hayashi, Ken Takasaki, Dongyun Yang, Kathleen D Danenberg, Peter V Danenberg
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 11 Issue 9 Pg. 3363-8 (May 01 2005) ISSN: 1078-0432 [Print] United States
• PMID: 15867236 (Publication Type: Clinical Trial, Journal Article)

Chemical References

• Antimetabolites, Antineoplastic
• Drug Combinations
• Membrane Proteins
• Pyridines
• RNA, Messenger
• S 1 (combination)
• Tegafur
• Oxonic Acid
• Cyclooxygenase 2
• PTGS2 protein, human
• Prostaglandin-Endoperoxide Synthases

Topics

• Aged
• Antimetabolites, Antineoplastic (therapeutic use)
• Colorectal Neoplasms (drug therapy, genetics, pathology)
• Cyclooxygenase 2
• Drug Combinations
• Female
• Gene Expression Regulation, Enzymologic (drug effects)
• Gene Expression Regulation, Neoplastic (drug effects)
• Humans
• Male
• Membrane Proteins
• Middle Aged
• Oxonic Acid (therapeutic use)
• Predictive Value of Tests
• Prognosis
• Prostaglandin-Endoperoxide Synthases (genetics)
• Pyridines (therapeutic use)
• RNA, Messenger (genetics, metabolism)
• Reverse Transcriptase Polymerase Chain Reaction
• Survival Analysis
• Tegafur (therapeutic use)
• Treatment Outcome