Skip to main content
Log in

Prospective controlled trial with antiestrogen drug tamoxifen in patients with unresectable hepatocellular carcinoma

  • Conference Report
  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript

Abstract

Clinical and experimental evidence indicates that estrogens are involved in the control of hepatocyte proliferation both in normal and in neoplastic conditions. Thirty-two cirrhotic patients with unresectable or otherwise untreatable hepatocellular carcinoma were allocated to receive either tamoxifen (30 mg/day) or no treatment. The patients in the two groups were matched for age, male/female ratio, Child-Pugh class, approximate tumor volume (US and CT scan), and etiology of the underlying cirrhosis. Survival of the tamoxifen-treated patients (life-table, Wilcoxon-Breslow) was significantly prolonged (P=0.0038), with 35% (vs 0%) survival at 12 months. No difference was observed between males and females or between alcoholic and nonalcoholic cirrhosis. In 40% of tamoxifen-treated patients, the levels of α-fetoprotein declined. In conclusion, the antiestrogen tamoxifen appears to be effective in the palliative treatment of hepatocellular carcinoma. An initial decline in α-fetoprotein levels may represent an early favorable prognostic sign.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

References

  1. Aldercrutz H, Tenhunen R: Some aspects of the interaction between natural and synthetic female sex hormones and the liver. Am J Med 49:630–648, 1970

    Google Scholar 

  2. Stauffer JQ, Lapinski MW, Harold DJ, Myers JK: Focal nodular hyperplasia of the liver and intrahepatic hemorrhage in young women on oral contraceptives. Ann Intern Med 83:301–306, 1975

    Google Scholar 

  3. Mays ET, Christopherson WM, Barrows GH: Focal nodular hyperplasia of the liver. Am J Clin Pathol 61:735–746, 1974

    Google Scholar 

  4. Christopherson WM, Mays ET, Barrows GH: Liver tumors in women on contraceptive steroids. Obstet Gynecol 46:221–223, 1975

    Google Scholar 

  5. Ameriks JA, Thompson NW, Frey CF, Appelman HD, Walter JF: Hepatic cell adenomas, spontaneous liver rupture and oral contraceptives. Arch Surg 110:548–557, 1975

    Google Scholar 

  6. Baum JK, Hlotz F, Bookstein JJ, Klein EW: Possible association between benign hepatomas and oral contraceptives. Lancet 2:926–929, 1973

    Google Scholar 

  7. O'Sullivan JP, Wilding RP: Liver hematomas in patients on contraceptives. Br Med J 3:7–10, 1974

    Google Scholar 

  8. Porter LE, Elm MS, Van Thiel DH, Eagon PK: Hepatic estrogen receptor in human liver disease. Gastroenterology 92:735–745, 1987

    Google Scholar 

  9. Macdonald JS, Lippman ME, Wooley PV, Petrucci PP, Schein PS: Hepatic estrogen and progesteron receptors in an estrogen-associated hepatic neoplasm. Cancer Chemother Pharmacol 1:135–138, 1978

    Google Scholar 

  10. Mays ET, Christopherson W: Hepatic tumors induced by sex steroids. Sem Liver Dis 4:147–157, 1984

    Google Scholar 

  11. Demanes DJ, Friedman MA, McKerrow JH, Hoffman PG: Hormone receptors in hepatoblastoma: A demonstration of both estrogens and progesterone receptors. Cancer 50:1828–1832, 1982

    Google Scholar 

  12. Ohnishi S, Murakami T, Moriyama T, Mitamura K, Imawari M: Androgen and estrogen receptors in hepatocellular carcinoma and in the surrounding noncancerous liver tissue. Hepatology 6:440–443, 1986

    Google Scholar 

  13. Kohigashi K, Fukuda Y, Imura H: Estrogen receptors in hepatocellular carcinoma: Is endocrine therapy for hepatocellular carcinoma likely to be effective? Gastroenterol Jpn 22:322–330, 1987

    Google Scholar 

  14. Reznik-Schuller H: Carcinogenic effects of diethylstilbestrol in male Syrian Golden hamster and European hamster. J Natl Cancer Inst 62:1083–1088, 1979

    Google Scholar 

  15. Li JJ, Li SA: High incidence of hepatocellular carcinoma after synthetic estrogens administration in Syrian Golden hamster fed α-naphthoflavone: A new tumor model. J Natl Cancer Inst 73:543–547, 1984

    Google Scholar 

  16. Heston W, Vlahakis A, Desmukes B: Effect of the antifertility drug Enovid in five strains of mice, with particular regard to carcinogenesis. J Natl Cancer Inst 51:209–224, 1973

    Google Scholar 

  17. Toh YC: Physiologic and biochemical reviews of sex difference and carcinogenesis with particular reference to the liver. Adv Cancer Res 18:155–156, 1973

    Google Scholar 

  18. Yager JD, Yager R: Oral contraceptive steroids as promoters of hepatocarcinogenesis in female Sprague-Dawley rats. Cancer Res 40:3680–3685, 1980

    Google Scholar 

  19. Sumi C, Yokoro K, Kajitani T, Ito A: Synergism of diethylstilbestrol and other carcinogens in concurrent development of hepatic, mammary, and pituitary tumors in castrated male rats. J Natl Cancer Inst 65:169–170, 1980

    Google Scholar 

  20. Schulte-Hermann R: Induction of liver growth by xenobiotic compounds and other stimuli. CRC Crit Rev Toxicol 3:97–98, 1979

    Google Scholar 

  21. Francavilla A, Di Leo A, Eagon PK, Wu SQ, Ove P, Van Thiel DH, Starzl TE: Regenerating rat liver: Correlation between estrogen receptor localization and deoxyribonucleic acid synthesis. Gastroenterology 86:562–567, 1984

    Google Scholar 

  22. Francavilla A, Polimeno L, Di Leo A, Barone M, Ove P, Coetzee M, Eagon P, Makowka L, Ambrosino G, Mazzaferro V, Starzl TE: The effect of tamoxifen on hepatocyte proliferationin vivo andin vitro. Hepatology 9:614–620, 1989

    Google Scholar 

  23. Okuda K, Peters RL, Simson WI: Gross anatomic features of hepatocellular carcinoma from three disparate geographic areas. Proposal of a new classification. Cancer 54:2165–2167, 1984

    Google Scholar 

  24. Melia WM, Johnson PJ, Williams R: Controlled clinical trial of doxorubicin and tamoxifen versus doxorubicin alone in hepatocellular carcinoma. Cancer Treat Rep 71(12):1213–1216, 1987

    Google Scholar 

  25. Guechot J, Peigney N, Ballet F, Vaubourdolle M, Giboudeau J, Poupon R: Sex hormone imbalance in male alcoholic cirrhotic patients with and without hepatocellular carcinoma. Cancer 62:760–762, 1988

    Google Scholar 

  26. Van Thiel DH, Lester R: The effect of chronic alcohol abuse on sexual function. Clin Endocrinol Metab 8:499–510, 1979

    Google Scholar 

  27. Eagon PK, Porter LE, Gavaler JS, Egler KM, Van Thiel DH: Effect of ethanol feeding upon levels of a male-specific hepatic estrogen binding protein: A possible mechanism for feminization. Alcoholism 5:183–187, 1981

    Google Scholar 

  28. Van Thiel DH, Gavaler JS: Ethanol and the endocrine system.In Alcohol-related Diseases in Gastoenterology. HK Seitz, B Kommerell (eds). Berlin, Springer-Verlag, 1985, pp 324–341

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Farinati, F., De Maria, N., Fornasiero, A. et al. Prospective controlled trial with antiestrogen drug tamoxifen in patients with unresectable hepatocellular carcinoma. Digest Dis Sci 37, 659–662 (1992). https://doi.org/10.1007/BF01296419

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01296419

Key Words

Navigation