Clinical

BJC Open article

British Journal of Cancer (2002) 86, 161–167. doi:10.1038/sj.bjc.6600048 www.bjcancer.com
Published online 21 January 2002

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

S Matsumoto1, Y Imaeda1, S Umemoto1, K Kobayashi1,2, H Suzuki1 and T Okamoto2

  1. 1Department of Surgery, Second Teaching Hospital, School of Medicine, Fujita Health University, 3-6-10 Otohbashi, Nakagawa-ku, Nagoya 454-8509, Japan
  2. 2Department of Molecular Genetics, Nagoya City University Medical School, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan

Correspondence: S Matsumoto, E-mail: smatsumo@fujita-hu.ac.jp

Received 14 June 2001; Revised 24 October 2001; Accepted 1 November 2001

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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 800mg day−1 of cimetidine orally together with 200mg 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.

Keywords:

colorectal cancer; cancer metastasis; sialyl Lewis antigens; cell adhesion; cimetidine