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Cimetidine increases survival of colorectal cancer patients with high levels of sialyl Lewis-X and sialyl Lewis-A epitope expression on tumour cells

Abstract

Cimetidine has been shown to have beneficial effects in colorectal cancer patients. In this 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−1 of cimetidine orally together with 200 mg day−1 of 5-fluorouracil, while the control group received 5-fluorouracil alone. The treatment was initiated 2 weeks after the operation and terminated after 1 year. Robust beneficial effects of cimetidine were noted: the 10-year survival rate of the cimetidine group was 84.6% whereas that of control group was 49.8% (P<0.0001). According to our previous observations that cimetidine blocked the expression of E-selectin on vascular endothelium and inhibited the adhesion of cancer cells to the endothelium, we have further stratified the patients according to the expression levels of sialyl Lewis antigens X (sLx) and A (sLa). We found that cimetidine treatment was particularly effective in patients whose tumour 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 tumours 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.)). These results clearly indicate that cimetidine treatment dramatically improved survival in colorectal cancer patients with tumour cells expressing high levels of sLx and sLa.

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Acknowledgements

We would like to thank K Saito for critical comments on the manuscript. We would also like to express our gratitude for cooperation of the Study Group of the Multicentre Clinical Study on cimetidine (Chair of Study Administration: S Matsumoto; Administrator, S Kodaira) involving 15 participating institutions (principal investigator): Fujita Health University, Second Teaching Hospital (S Matsumoto, S Umemoto), Fujita Health University Hospital (M Ochiai), Hamamatsu Medical School (S Baba), Hamamatsu Red Cross Hospital (K Okuda, M Sumiyama), Shizuoka Red Cross Hospital (J Miyata, K Ando), Toyota Chiiki Medical Centre (A Seto), Orido Hospital (K Takayama), Ooshima Hospital (K Nagai), Ootawara Red Cross Hospital (T Amemiya), Haga Red Cross Hospital (M Kojima), Mito Red Cross Hospital (M Sakuma), Saitama Chuo Hospital (K Maeda, Y Hosoda), Inagi City Hospital (E Kurihara), Kawasaki City Ida Hospital (S Sadahiro, H Kawahara), Teikyo University Hospital (S Kodaira). This work was supported in part by grants-in-aids for Scientific Research from the Ministry of Education, Science, Sports, and Culture and the Ministry of Health and Human Welfare in Japan.

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Matsumoto, S., Imaeda, Y., Umemoto, S. et al. Cimetidine increases survival of colorectal cancer patients with high levels of sialyl Lewis-X and sialyl Lewis-A epitope expression on tumour cells. Br J Cancer 86, 161–167 (2002). https://doi.org/10.1038/sj.bjc.6600048

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