Survival of colorectal cancer patients with high levels of sialyl lewis-x and sialyl lewis-a epitope expression on tumor cells was improved by cimetidine

SM Matsumoto, MD, PhD

Fujita Health University, Second Teaching Hospital, Nagoya, Aichi Japan

Aim: In our previous study, a total of 64 colorectal cancer patients who received curative operation were examined for the effects of cimetidine treatment on survival and recurrence. The cimetidine group was given 800 mg/day of cimetidine orally together with 200 mg/day of 5-FU, while the control group received 5-FU alone. The treatment was initiated two weeks after the operation and terminated after one year. Beneficial effects of cimetidine were noted: the 10-year survival rate of the cimetidine group was 76.2% whereas that of control group was 46.7% (p<0.0001). According to our findings that cimetidine blocked the expression of E-selectin on vascular endothelium and inhibited the adhesion of cancer cells to the endothelium (Kobayashi, et al. Cancer Res. 60,3978-3984,2000), we intended to examine the effect of cimetidine on the degree of expression of sialyl Lewis antigens, which were counter-molecules of E-selectin. Methods: we have further stratified the patients According to the expression levels of sialyl Lewis antigens X (sLx) and A (sLa). Results: we found that cimetidine treatment was particularly effective in patients whose tumor had higher sLx and sLa antigen levels. For example, the 10-year cumulative survival rate of the cimetidine group with higher CSLEX staining, recognizing sLx, of tumors was 95.5%, whereas that of control group was 35.1% (p=0.0001). In contrast, in the group of patients with no or low levels CSLEX staining, cimetidine did not show significant beneficial effect (the 10-year survival rate of the cimetidine group was 70.0%, and that of control group was 85.7% (p=n.s.)). Conclusions: these results clearly indicate that cimetidine treatment dramatically improved survival in colorectal cancer patients with tumor cells expressing high levels of sLx and sLa.

KEY WORDS: cimetidine, survival, colorectal cancer, sialyl Lewis-X, sialyl Lewis-A.

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Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Paris, France; February 9 - 12, 2002; in the section on Novel Therapies, Part 2.

This presentation was a winner in our poster contest and was recognized with the Symposium Presidents' Award for Scientific Excellence.