Randomized trial of preoperative cimetidine in patients with colorectal carcinoma with quantitative assessment of tumor-associated lymphocytes

BACKGROUND. Previous studies have suggested that cimetidine, a histamine-2 receptor antagonist with immunostimulatory effects, may improve survival in patients with colorectal carcinoma. This effect may be apparent by an incr ease in the number of peritumoral lymphocytes. A prospective, double blind, randomized, placebo-controlled trial of a short course of preoperative tre atment with cimetidine in patients with colorectal carcinoma was performed to assess the effect of cimetidine on survival and on the number of peritum oral lymphocytes. METHODS. One hundred and twenty-five patients who were scheduled to undergo elective colon or rectal excision for carcinoma were randomized to receive either placebo or cimetidine preoperatively for 5 days. In addition to sta ndard histopathology, immunohistochemistry and computer video image analysi s were used to assess the number of peritumoral lymphocytes in an objective manner. Interim survival analysis according to the Kaplan-Meier method was performed. RESULTS. A trend toward a survival advantage in the group of patients recei ving cimetidine (800 mg twice daily) compared with the placebo group was ob served (P = 0.20, log rank test) that was most marked in patients with repl ication error negative tumors (P = 0.04). Similarly, in these two groups th ere was a trend toward an increase in the number of patients with a conspic uous lymphocytic infiltration (P = 0.10, chi-square test). However, there w as no difference in the number of peritumoral lymphocytes as measured by im age analysis. CONCLUSIONS. Based on the results of the current study, a short course of p reoperative treatment with cimetidine does appear to have an effect on pati ent survival; however, the exact mechanism is unknown. The failure of this study to demonstrate a clear increase in the local lymphocyte response does not exclude an immunologic mechanism of action. (C) 1999 American Cancer S ociety.