Background: Evidence first appeared in 1988 that cimetidine as an adjuvant may improve the survival of severely ill gastro-intestinal cancer patients when given peri- or postoperatively. Since then, several studies have appeared which suggest an anticancer activity for cimetidine, although few attempts have been made to corroborate their findings in large, placebo-controlled, double-blind studies. Method: We reviewed the literature concerning cimetidine’s potential anticancer activity, particularly with regard to gastro-intestinal cancers. Results: Most studies suggest that cimetidine may improve the outcome in cancer patients by a three-pronged mechanism involving (1) inhibition of cancer cell proliferation; (2) stimulation of the lymphocyte activity by inhibition of T cell suppressor function, and (3) inhibition of histamine’s activity as a growth factor in tumours. Conclusion: Bearing in mind the experimental evidence, as well as the potential and excellent safety profile of cimetidine, more studies are required and justified to clarify cimetidine’s protherapeutic activity.

1.
Moller H, Lindvig K, Klefter R, Mosbech J, Moller Jensen O: Cancer occurrence in a cohort of patients treated with cimetidine. Gut 1989;30:1558–1562.
[PubMed]
2.
Correa, P: A human model of gastric carcinogenesis. Cancer Res 1988;48:3554–3560.
[PubMed]
3.
Streett CS, Cimprich RE, Robertson JL: Pathologic findings in the stomachs of rats treated with the H2-receptor antagonist tiotidine. Scand J Gastroenterol Suppl 1984;101:109–117.
[PubMed]
4.
Moller H, Nissen A, Mosbech J: Use of cimetidine and other peptic ulcer drugs in Denmark 1977–1990 with analysis of the risk of gastric cancer among cimetidine users. Gut 1992;33:1166–1169.
[PubMed]
5.
Burtin C, Noirot C, Scheinmann P, Galoppin L, Domagoj S, Bernard P: Clinical improvement in advanced cancer disease after treatment combining histamine and H2 histaminics (ranitidine or cimetidine). Eur J Cancer Clin Oncol 1988;21:161–167.
6.
Tonnesen H, Knigge UP, Bulow S, Damm P, Fischerman K, Hesselfeldt P, Hjortrup A: Cimetidine treatment of stomach cancer. Ugeskr Læger 1989;151:1549–1551.
7.
Taylor TV et al: Healing of a malignant gastric ulcer with cimetidine. J R Coll Surg Edinb 1988;33:339–340.
[PubMed]
8.
Adams WJ, Morris DL: Short-course cimetidine and survival with colorectal cancer. Lancet 1994;1344:1768–1769.
9.
Matsumoto S: Cimetidine and survival with colorectal cancer. Lancet 1995;346:115.
10.
Links M, Clingan PR, Phadke K, O’Baugh J, Legge J, Adams WJ, Ross WB, Morris DL: A randomized trial of cimetidine with 5-fluorouracil and folinic acid in metastatic colorectal cancer. Eur J Surg Oncol 1995;21:523–525.
[PubMed]
11.
Svendsen LB, Ross C, Knigge U, Frederiksen HJ, Graversen P, Kjærgard J, Luke M, Stimpel H, Sparso BH: Cimetidine as an adjuvant treatment in colorectal cancer. A double-blind, randomized pilot study. Dis Colon Rectum 1995;38:514–518.
[PubMed]
12.
Primrose JN, Miller GV, Preston SR, Gokhale J, Ambrose NS, Ward UM, Mills JG, Ebsanullah RSB, Darekar B: A prospective randomised controlled study of the use of ranitidine in patients with gastric cancer. Gut 1998;42:17–19.
[PubMed]
13.
Adams WJ, Lawson JA, Nicholson SE, Cook TA, Morris DL: The growth of carcinogen-induced colon cancer in rats is inhibited by cimetidine. Eur J Surg Oncol 1993;19:332–335.
[PubMed]
14.
Adams WJ, Lawson JA, Morris DL: Cimetidine inhibits in vivo growth of human colon cancer and reverses histamine stimulated in vitro and in vivo growth. Gut 1994;35:1632–1636.
[PubMed]
15.
Lawson JA, Adams WJ, Morris DL: Ranitidine and cimetidine differ in their in vitro and in vivo effects on human colonic cancer growth. Br J Cancer 1993;73:872–876.
16.
Watson SA, Wilkinson LJ, Robertson JFR, Hardcastle JD: Effect of histamine on the growth of human gastrointestinal tumours: Reversal by cimetidine. Gut 1993;34:1091–1096.
[PubMed]
17.
Morris DL, Adams WJ: Cimetidine and colorectal cancer – old drug, new use. Nat Med 1995;1:1243–1244.
[PubMed]
18.
Garcia-Cabellero M, Nunezed X, Castro I, Kusche J, Vora Thorbeck L: Histamine metabolism in human breast and colorectal cancer: Its effects on other host tissues. Adv Biosci 1993;89:273–287.
19.
Jeziorska M, Haboubi NY, Schofield PF, Wooley DE: Mast cell distribution and tumour cell proliferation in colonic carcinoma. Gut 1993;34:55.
20.
Traiffort E, Pollard H, Moreau J, Ruat M, Schwartz JC, Martinez-Mir MI, Palacios JM: Pharmacological characterization and autoradiographic localization of histamine H2 receptors in human brain identified with [125I]iodoaminopotentidine. J Neurochem 1992;59:290–299.
[PubMed]
21.
Nanda NK, Nath I: Characteristics of histamine receptors present on suppressor T cells in ‘healthy individuals’. Scand J Gastroenterol 1995;30:265–271.
[PubMed]
22.
Siegers CP, Hiltl DM, Stich R: Cimetidine hemmt das Tumorzellwachstum, Therapiewoche 1995;36:2110–2114.
23.
Hahm KB, Park IS, Kim HC, Lee KJ, Kim JH, Cho SW, Lee SI: Comparison of antiproliferative effects of 1-histamine-2 receptor antagonists, cimetidine, ranitidine, and famotidine, in gastric cancer cells. Int J Immunopharmacol 1996;18:393–399.
[PubMed]
24.
Hahm KB, Kim WH, Lee SI, Kang JK, Park IS: Comparison of immunomodulative effects of the histamine-2 receptor antagonists cimetidine, ranitidine, and famotidine on peripheral blood mononuclear cells in gastric cancer patients. Int J Immunopharmacol 1994;16:985–993.
[PubMed]
25.
Wen QS, Zhang GZ, Kong XT: Modulation effect of cimetidine on the production of IL–2 and interferon-gamma in patients with gastric cancer. Leukemia 1994;8:(suppl):121–126.
26.
Adams WJ, Morris DL: Pilot study – cimetidine enhances lymphocyte infiltration of human colorectal carcinoma: Results of a small randomized control trial. 1997;80:15–21.
27.
Hansbrough J, Zapata-Sirvent R, Bender E: Prevention of alterations in postoperative lymphocyte subpopulations by cimetidine and ibuprofen. Am J Surg 1986;151:249–255.
[PubMed]
28.
Smith T: Histamine type 2 receptor antagonists and cancer immunotherapy. Compr Ther 1990;16:8–13.
29.
Flodgren P, Borgström S, Jonsson PE, Lindström C, Sjögren HO: Metastatic malignant melanoma: Regression induced by combined treatment with interferon [HuIFN-alpha(Le)] and cimetidine. Int J Cancer 1983;32:657–665.
[PubMed]
30.
Creagan ET, Schaid DJ, Ahmann DL, Frytak S: Disseminated malignant melanoma and recombinant interferon: Analysis of seven consecutive phase II investigations. J Invest Dermatol 1990;95(suppl):188–192.
31.
Marshall ME, Mendelsohn L, Butler K, Riley L, Cantrell J, Wiseman C, Taylor R, Macdonald JS: Treatment of metastatic renal cell carcinoma with coumarin (1,2-benzopyrone) and cimetidine: A pilot study. J Clin Oncol 1987;5:862–866.
[PubMed]
32.
Kinouchi T, Saiki S, Maeda O, Kuroda M, Usami M, Kotake T: Treatment of advanced renal cell carcinoma with a combination of human lymphoblastoid interferon-alpha and cimetidine. J Urol 1997;157:1604–1607.
[PubMed]
33.
Sagaster P, Micksche M, Flamm J, Ludwig H: Randomised study using IFN-alpha versus IFN-alpha plus coumarin and cimetidine for treatment of advanced renal cell cancer. Ann Oncol 1995;6:999–1003.
[PubMed]
34.
Inhorn L, Williams SD, Nattam S, Stephens D: High-dose cimetidine for the treatment of metastatic renal cell carcinoma. A Hoosier Oncology Group study. Am J Clin Oncol 1992;15:157–159.
[PubMed]
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