542P - Down-regulation of γ-glutamyl hydrolase gene expression in tumor tissues is associated with response to oral uracil and tegafur/leucovorin chemothe...

Date 01 October 2012
Event ESMO Congress 2012
Session Poster presentation III
Topics Colon Cancer
Rectal Cancer
Presenter Sotaro Sadahiro
Authors S. Sadahiro1, T. Suzuki1, A. Tanaka1, K. Okada1, A. Kamijo1, H. Nagase2, J. Uchida2
  • 1Gastrointestinal Surgery, Tokai University School of Medicine, 259-1193 - Isehara/JP
  • 2Tokushima Research Center, Taiho Pharmaceutical Co., Ltd., 771-0194 - Tokushima/JP

Abstract

Background

5-Flurouracil (5-FU)/leucovorin (LV) and oral uracil and tegafur (UFT)/LV are widely used as standard adjuvant chemotherapy for colorectal cancer (CRC). We previously reported that right-sided tumors with high thymidine phosphorylase (TP) gene expression on pre-chemotherapy tumor biopsy are associated with a response to UFT/LV chemotherapy in patients with CRC. In the present study, we examined the relation between chemotherapy-induced gene expression changes (post-chemotherapy/pre-chemotherapy gene expression ratio) in CRC tissues and the efficacy of UFT/LV treatment.

Material and methods

The subjects were 73 patients with CRC who were scheduled to undergo surgery. UFT (300 mg/m2/day) and LV (75 mg/day) were administered for 2 weeks before surgery. We assessed pathological response based on the extent of residual cancer cells and granulation tissue. The mRNA expressions of 6 pyrimidine-related enzymes and 8 reduced folate-related enzymes were quantitatively evaluated using a RT-PCR assay in paired samples of pre-chemotherapy tumor-biopsy specimens and post-chemotherapy resected-tumor specimens.

Results

Pathological responses were observed in 19.2% (14/73) of the patients. Gene expression of γ-glutamyl hydrolase (GGH) was generally down-regulated after chemotherapy, and the extent of GGH down-regulation among the responders was significantly greater than that among the non-responders, with the least p value of 0.0009 among the genes studied. The extent of GGH down-regulation among right-sided tumors with high sensitivity to UFT/LV chemotherapy was significantly greater than that among left-sided tumors (p = 0.0135). Moreover, on combined analysis of tumor site and sex, the extent of GGH down-regulation among left-sided tumors in men that showed low sensitivity to UFT/LV chemotherapy was significantly smaller than that among other tumors (p = 0.0018).

Conclusion

Down-regulation of GGH gene expression in primary CRC tissues after UFT/LV chemotherapy is associated with a response to chemotherapy in patients with CRC.

Disclosure

H. Nagase: He is an employee of Taiho Pharmaceutical Co.

J. Uchida: He is an employee of Taiho Pharmaceutical Co.

All other authors have declared no conflicts of interest.