Pilot study-Cimetidine enhances lymphocyte infiltration of human colorectal carcinoma: Results of a small randomized control trial

Adams and Morris1 found that preoperative cimetidine induced a positive lymphocyte response in 5 of 24 colorectal carcinoma patients not treated with cimetidine and in 10 of 18 carcinoma patients treated with the drug, and suggested that cimetidine antagonized histamine inhibition of lymphocyte function at a histamine H2 receptor by increasing lymphocyte infiltrate in human colorectal carcinoma.1 They had also previously shown that cimetidine administered preoperatively improved the survival of colorectal carcinoma patients, suggesting a protective role of cimetidine against intestinal carcinogenesis.2 However, this finding is still uncertain both in humans3, 4 and in laboratory animals.5 A 10-year postmarketing surveillance of the safety of cimetidine reported significant excess mortality (RR = 2.7, based on 35 deaths) in the first year. However, this leveled off with time, and the point estimates for colorectal carcinoma were not significantly below unity after 5 years.6 Thus, the data on a possible relation between cimetidine therapy and colorectal carcinogenesis are still inconclusive. Therefore, we assessed the relation between cimetidine use and the risk of colorectal carcinoma in a large case-control study carried out in Northern Italy between 1985 and 1991.7 The cases comprised 955 patients with incident, histologically confirmed carcinoma of the colon (498 men and 457 women; median age, 61 years; range, 20-79 years) and 639 with carcinoma of the rectum (380 men and 259 women; median age, 62 years; range, 20-79 years). Controls comprised 2909 patients (1880 men and 1029 women; median age, 58 years; range, 19-79 years) admitted to the same hospitals for various acute conditions not related to digestive tract diseases or to known or likely risk factors for colorectal carcinoma. A total of 29 cases of colon carcinoma (3.0%), 17 cases of rectal carcinoma (2.7%), and 106 controls (3.6%) reported use of cimetidine (Table 1). The multivariate odds ratios (ORs) were 0.9 for colon carcinoma and 0.8 for rectal carcinoma. There was no relation with time since the first use of the drug: the OR for colon carcinoma was 0.8 for use that began either ≤7 or >7 years earlier, and the ORs for rectal carcinoma were 0.7 and 1.0 for use that began ≤7 or >7 years earlier, respectively. Thus, these findings rule out a major relation between cimetidine use and colorectal carcinoma risk, although they are compatible with a moderate favorable effect. Alessandra Tavani*, Francesca Fioretti*, Silvia Franceschi , Carlo La Vecchia