Prospective, double-blind, placebo-controlled randomized trial of cimetidine in gastric cancer

Abstract

Summary Cimetidine is thought to inhibit suppressor T-lymphocyte function and preliminary evidence from a randomized trial indicated that it might prolong survival for patients with operable and inoperable gastric cancer. The British Stomach Cancer Group conducted a randomized, double-blind, placebo-controlled trial examining the effects of cimetidine (400 mg or 800 mg twice a day) on the survival of patients with early (stages I, II and III: n = 229) and advanced (stages IVa and IVb: n = 201) gastric cancer. The primary end point was death. A total of 442 patients were randomized by 59 consultants in 39 hospitals between February 1990 and March 1995. Log-rank survival analysis was used to assess differences between the groups. Three hundred and forty patients died during the study: 166 (49%) in the cimetidine treatment groups and 174 (51%) in the placebo groups. Median survival for patients receiving cimetidine was 13 months (95% confidence interval (CI) 9-16 months) and 11 months in the placebo arm (95% CI 9-14 months). There was no significant difference in survival between the two treatment groups (P = 0.42) or between different doses of cimetidine tablets (P = 0.46). Five-year survival of those patients randomized to cimetidine was 21% compared to 18% for those patients randomized to placebo. Cimetidine at a dose of 400 mg or 800 mg twice a day does not have a significant influence on the survival of patients with gastric cancer compared to placebo.

Why is the coexistence of gastric cancer and duodenal ulcer rare? Examination of factors related to both gastric cancer and duodenal ulcer

“…3), and noted that the perioperative use of cimetidine in gastric cancer patients could help restore diminished cellular immunity. Milito and Fais [43], Dillman et al [44], and Jiang et al [45] were in agreement with this opinion, but Langman et al [46] reported that cimetidine did not show significantly more influence on the survival of patients with gastric cancer than placebo. Therefore, further investigation is required into the effects of cimetidine.…”

Effect of Pre-Operative Short Course Famotidine on Tumor Infiltrating Lymphocytes in Colorectal Cancer: A Double Blind, Placebo Controlled, Prospective Randomized Study

“…In another report, pre-operative cimetidine led to significant lymphocytic infiltration in colorectal tumors [21]. However, three recent randomized trials in gastric cancer and one large randomized Danish study in colorectal cancer patients, who received ranitidine post-operatively, showed no overall survival benefit [22][23][24][25]. A subgroup analysis in the Danish study showed a survival benefit for patients who received ranitidine but did not receive blood transfusions nor developed post-operative infectious complications [26].…”

Cimetidine inhibits the adhesion of gastric cancer cells expressing high levels of sialyl Lewis x in human vascular endothelial cells by blocking E-selectin expression

“…In 1988 it was reported that post-operative treatment with cimetidine improved survival of patients with any stage of gastric cancer (10). But, in a more recent and larger study organized by the British Stomach Cancer Group, cimetidine had no effect on survival when compared to the placebo group (11). Recently, Kobayashi et al (12) showed that cimetidine could block the adhesion of a colorectal tumor cell line to endothelial cells in vitro and could suppress the formation of hepatic metastasis in a nude mouse model via the down-regulation of the cell surface expression of the adhesion molecule E-selectin on endothelial cells.…”