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

Cancer. 1999 Apr 15;85(8):1658-63. doi: 10.1002/(sici)1097-0142(19990415)85:8<1658::aid-cncr3>3.0.co;2-q.

Abstract

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 increase in the number of peritumoral lymphocytes. A prospective, double blind, randomized, placebo-controlled trial of a short course of preoperative treatment with cimetidine in patients with colorectal carcinoma was performed to assess the effect of cimetidine on survival and on the number of peritumoral 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 standard histopathology, immunohistochemistry and computer video image analysis 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 receiving cimetidine (800 mg twice daily) compared with the placebo group was observed (P = 0.20, log rank test) that was most marked in patients with replication error negative tumors (P = 0.04). Similarly, in these two groups there was a trend toward an increase in the number of patients with a conspicuous lymphocytic infiltration (P = 0.10, chi-square test). However, there was no difference in the number of peritumoral lymphocytes as measured by image analysis.

Conclusions: Based on the results of the current study, a short course of preoperative treatment with cimetidine does appear to have an effect on patient 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.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / administration & dosage
  • Adjuvants, Immunologic / pharmacology
  • Adjuvants, Immunologic / therapeutic use*
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Carcinoma / immunology
  • Carcinoma / mortality
  • Carcinoma / pathology
  • Carcinoma / surgery*
  • Cimetidine / pharmacology
  • Cimetidine / therapeutic use*
  • Colorectal Neoplasms / immunology
  • Colorectal Neoplasms / mortality
  • Colorectal Neoplasms / pathology
  • Colorectal Neoplasms / surgery*
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Histamine H2 Antagonists / administration & dosage
  • Histamine H2 Antagonists / pharmacology
  • Histamine H2 Antagonists / therapeutic use*
  • Humans
  • Image Processing, Computer-Assisted
  • Immunophenotyping
  • Life Tables
  • Lymphocyte Count
  • Lymphocytes, Tumor-Infiltrating / drug effects*
  • Premedication*
  • Preoperative Care*
  • Survival Analysis
  • Treatment Outcome

Substances

  • Adjuvants, Immunologic
  • Antineoplastic Agents
  • Histamine H2 Antagonists
  • Cimetidine