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Cimetidine as an adjuvant treatment in colorectal cancer

A double-blind, randomized pilot study

  • Original Contributions
  • Published:
Diseases of the Colon & Rectum

Abstract

PURPOSE: To evaluate the influence of a H 2 receptor antagonist (cimetidine) on survival in patients with colorectal carcinoma, a randomized, controlled pilot study was performed in three university hospitals in Copenhagen, Denmark. METHODS: A total of 192 patients, who had undergone a resection or an exploratory operation for adenocarcinoma of the colon or rectum between May 1988 and May 1991, were enrolled in the study. After a median observation time of 40 months, outcome was noted for each patient concerning cancer-specific mortality rate. RESULTS: In patients operated with curative intent (n=148), no difference was found in cancer-specific mortality between the two treatments. However, a tendency toward reduction in mortality rate was found in patients with curatively operated Dukes Stage C carcinoma (P=0.11, log-rank test; difference, 29 percent; 90 percent confidence interval, 2 to 57 percent) in the cimetidine-treated group. In patients with disseminated disease no total difference was found between the two treatment groups. CONCLUSIONS: Cimetidine does not seem to reduce mortality in patients with colorectal cancer, but there seems to be a tendency toward a survival benefit in patients undergoing surgery for Dukes Stage C carcinoma. Results seem to justify trials in this patient catagory to reveal a benefit of H2 receptor antagonists in adjuvant therapy of colorectal carcinoma.

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References

  1. Storm HH, Mandres T, Friis S, Bang S. Cancer incidence in Denmark 1989. Copenhagen: Danish Cancer Society, 1989;24.

    Google Scholar 

  2. Griffin MR, Bergstalh EJ, Coffey RJ, Beart RW Jr, Melton LJ III. Predictors of survival after curative resection of carcinoma of the colon and rectum. Cancer 1987;60: 2318–24.

    PubMed  Google Scholar 

  3. Olson RM, Perencevich NP, Malcolm AW, Chaffey JT, Wilson RE. Patterns of recurrence following curative resection of adenocarcinoma of the colon and rectum. Cancer 1980;45:2969–74.

    PubMed  Google Scholar 

  4. Svendsen LB, Sørensen C, Kjersgaard P, Meisner S, Kjærgård J. The influence of age upon curative operation for colorectal cancer. Int J Colorectal Dis 1989;4: 123–7.

    Article  PubMed  Google Scholar 

  5. Metzger U. Adjuvant therapy for colorectal carcinoma. World J Surg 1991;15:576–82.

    Article  PubMed  Google Scholar 

  6. Moertel CG, Fleming TR, MacDonald JS,et al. Levamisole and fluorouracil for adjuvant therapy of resected colon carcinoma. N Engl J Med 1990;322:352–8.

    PubMed  Google Scholar 

  7. Wunderlich M, Schiessel R, Rainer H,et al. Effect of adjuvant chemotherapy—or immunotherapy on the prognosis of colorectal cancer operated for cure. Br J Surg 1985;(Suppl):S107-S110.

    Google Scholar 

  8. Barkla DH, Tutton PJ. Influence of histamine and serotonin antagonists on the growth of xenografted human colorectal tumors. J Natl Cancer Inst 1981;67:1207–11.

    PubMed  Google Scholar 

  9. Burtin C, Noirot C, Scheinemann P, Galoppin L, Sabolovic D, Bernard P. Clinical improvement in advanced cancer disease after treatment combining histamine and H-2 antihistaminics (ranitidine and cimetidine). Eur J Cancer Clin Oncol 1988;24:161–7.

    Article  PubMed  Google Scholar 

  10. Gifford RR, Voss BV, Ferguson RM. Cimetidine protection against lethal tumor challenge in mice. Surgery 1981;90:344–51.

    PubMed  Google Scholar 

  11. Osband ME, Shen Y, Schlesinger M,et al. Successful tumor immunotherapy with cimetidine in mice. Lancet 1981;1:636–8.

    Article  PubMed  Google Scholar 

  12. Tønnesen H, Knigge U, Bülow S,et al. Effect of cimetidine on survival after gastric cancer. Lancet 1988;2: 990–1.

    PubMed  Google Scholar 

  13. Dukes CE. The classification of cancer of the rectum. J Pathol 1932;35:323–33.

    Article  Google Scholar 

  14. Peto R, Pike MC, Armitage P,et al. Design and analysis of randomized clinical trials requiring prolonged observations of each patient. Br J Cancer 1976;34:585–612.

    PubMed  Google Scholar 

  15. Machin D, Gardner MJ. Calculating confidence intervals for survival time analysis. BMJ 1988;296:1366–71.

    Google Scholar 

  16. Bartholeyn J, Fozard JR. Role of histamine in tumor development. Trends Pharmacol Sci 1985;6:123–5.

    Article  Google Scholar 

  17. Garcia-Caballero M, Neugebauer E, Campos R, Nunez de Castro J, Vara-Thorbeck C. Increased histidine decarboxylase (HDC) activity in human colorectal cancer: results of a study on ten patients. Agents Actions 1988;23:357–60.

    Article  PubMed  Google Scholar 

  18. Moriarty CM, Stucky JL, Hamburger KW, Patil KD, Foley JF, Koefoot RR. Blood histamine and solid malignant tumors. J Cancer Res Clin Oncol 1988;114:588–92.

    Article  PubMed  Google Scholar 

  19. Cole WH, Humphrey L. Need for immunologic stimulation during immunosuppression produced by major cancer surgery. Ann Surg 1985;202:9–20.

    PubMed  Google Scholar 

  20. Sugarbaker PH. A perspective on the clinical research strategies in carcinoma of the large bowel. World J Surg 1991;15:609–16.

    Article  PubMed  Google Scholar 

  21. Weese JL, Ottery FD, Emoto SE. Do operations facilitate tumor growth? An experimental model in rats. Surgery 1986;100:273–7.

    PubMed  Google Scholar 

  22. Tilly BC, Terloolen LG, Remori R,et al. Histamine as a growth factor and chemoattractant for human carcinoma and melanoma cells: action through Ca2+- mobilizing H1 receptors. J Cell Biol 1990;110:1211–5.

    Article  PubMed  Google Scholar 

  23. Nielsen HJ, Hammer JH, Moesgaard F, Kehlet H. Possible role of histamine-2 receptor antagonists for adjuvant treatment in colorectal cancer. Eur J Surg 1991;157:437–41.

    PubMed  Google Scholar 

  24. Balch CM, Dougherty PA, Cloud GA, Tilden AB. Prostaglandin E-2 mediated suppression of cellular immunity in colon cancer patients. Surgery 1984;95:71–6.

    PubMed  Google Scholar 

  25. Kojima O, Fujita Y, Iwai N,et al. Studies on cell mediated immunity in patients with colorectal cancer: leucocyte migration inhibition test using allogenic 3 M KCl extract. Aust N Z J Surg 1981;51:434–9.

    PubMed  Google Scholar 

  26. Hammer JH, Nielsen HJ, Moesgaard F, Kehlet H. Duration of postoperative immunosuppression assessed by repeated delayed type hypersensitivity skin tests. Eur Surg Res 1992;24:133–7.

    PubMed  Google Scholar 

  27. Hansbrough JH, Zapata-Sirvent RL, Bender EM. Prevention of alterations in postoperative lymphocyte subpopulations by cimetidine and ibuprofen. Am J Surg 1986;151:249–55.

    Article  PubMed  Google Scholar 

  28. Windle R, Bell PR, Shaw D. Five years results of a randomized trial of adjuvant 5-fluorouracil and levamisole in colorectal cancer. Br J Surg 1987;74:569–72.

    PubMed  Google Scholar 

  29. Laurie JA, Moertel CG, Fleming TR,et al. Surgical adjuvant therapy of the large bowel carcinoma: an evaluation of levamisole and the combination of levamisole and fluorouracil. J Clin Oncol 1989;7:1447–56.

    PubMed  Google Scholar 

  30. Wanebo HJ, Jun MY, Strong EW, Oettgen H. T-cell deficiency in patients with squamous cell cancer of the head and neck. Am J Surg 1975;130:445–51.

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Gastrointestinal Surgery, Bispebjerg Hospital, Blegdamsvej 9, DK 2100, Copenhagen Ø, Denmark

    Hans Jørgen Frederiksen M.D., Johan Kjærgåfrd M.D., M.D.Sci, Michael Luke M.D. & Bo Hempel Sparsø M.D.

  2. Department of Gastrointestinal Surgery, Frederiksberg Hospital, Blegdamsvej 9, DK 2100, Copenhagen Ø, Denmark

    Christian Ross M.D., Ulrich Knigge M.D., M.D.Sci., Peter Graversen M.D. & Hans Stimpel M.D.

  3. Department of Gastrointestinal Surgery C 2122, Rigshospitalet, Blegdamsvej 9, DK 2100, Copenhagen Ø, Denmark

    Lars Bo Svendsen M.D., M.D.Sci.

Authors
  1. Lars Bo Svendsen M.D., M.D.Sci.
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  2. Christian Ross M.D.
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  3. Ulrich Knigge M.D., M.D.Sci.
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  4. Hans Jørgen Frederiksen M.D.
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  5. Peter Graversen M.D.
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  6. Johan Kjærgåfrd M.D., M.D.Sci
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  7. Michael Luke M.D.
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  8. Hans Stimpel M.D.
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  9. Bo Hempel Sparsø M.D.
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Additional information

Read at the XII International Congress of Pharmacology, Winnipeg, Montreal, Canada, July, 1994.

Cimetidine and placebo tablets were supplied by GEA Ltd., Copenhagen, Denmark.

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Svendsen, L.B., Ross, C., Knigge, U. et al. Cimetidine as an adjuvant treatment in colorectal cancer. Dis Colon Rectum 38, 514–518 (1995). https://doi.org/10.1007/BF02148852

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