Skip to main content
NCBI home page
British Journal of Cancer logoLink to British Journal of Cancer
. 2001 Apr;84(7):881–885. doi: 10.1054/bjoc.2000.1534

Hormonal therapy with megestrol in inoperable hepatocellular carcinoma characterized by variant oestrogen receptors

E Villa 1, I Ferretti 1, A Grottola 1, P Buttafoco 1, M Grazia Del Buono 1, F Giannini 1, M Manno 1, H Bertani 1, A Dugani 1, F Manenti 1
PMCID: PMC2363845  PMID: 11286465

Abstract

Variant liver oestrogen receptor transcripts in hepatocellular carcinoma are associated with aggressive clinical course and unresponsiveness to tamoxifen. To evaluate the impact on survival and on tumour growth of megestrol (progestin drug acting at post-receptorial level) we enrolled 45 patients with HCC characterized by variant liver oestrogen receptors in a prospective, randomized study with megestrol vs. placebo. Presence of variant oestrogen receptors was determined by RT/PCR. 24 patients were randomized to no treatment and 21 to therapy with megestrol 160 mg day−1. Results were analysed by Kaplan-Meier and Cox methods. Survival of hepatocellular carcinoma characterized by variant oestrogen receptors was extremely poor (median survival 7 months); megestrol significantly improved survival (18 months) (P = 0.0090). Tumour growth at one year was significantly slowed down in megestrol-treated patients (P = 0.0212). Bilirubin levels, presence of portal thrombosis, HBV aetiology and treatment were identified at univariate analysis as factors significantly associated with survival; at multivariate analysis, only megestrol therapy (P = 0.0003), presence of HBV infection (P = 0.0009) and presence of portal vein thrombosis (P = 0.0051) were factors independently related with survival. (1) Megestrol slows down the aggressive tumour growth of patients with hepatocellular carcinoma characterized by variant estrogen receptors and (2) is also able to favourably influence the course of disease, more than doubling median survival. © 2001 Cancer Research Campaignhttp://www.bjcancer.com

Keywords: variant liver oestrogen receptors transcripts, hepatocellular carcinoma, tamoxifen, megestrol

Full Text

The Full Text of this article is available as a PDF (85.9 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Castells A., Bruix J., Bru C., Fuster J., Vilana R., Navasa M., Ayuso C., Boix L., Visa J., Rodés J. Treatment of small hepatocellular carcinoma in cirrhotic patients: a cohort study comparing surgical resection and percutaneous ethanol injection. Hepatology. 1993 Nov;18(5):1121–1126. [PubMed] [Google Scholar]
  2. Castells A., Bruix J., Brú C., Ayuso C., Roca M., Boix L., Vilana R., Rodés J. Treatment of hepatocellular carcinoma with tamoxifen: a double-blind placebo-controlled trial in 120 patients. Gastroenterology. 1995 Sep;109(3):917–922. doi: 10.1016/0016-5085(95)90402-6. [DOI] [PubMed] [Google Scholar]
  3. Chao Y., Chan W. K., Wang S. S., Lai K. H., Chi C. W., Lin C. Y., Chan A., Whang-Peng J., Lui W. Y., Lee S. D. Phase II study of megestrol acetate in the treatment of hepatocellular carcinoma. J Gastroenterol Hepatol. 1997 Apr;12(4):277–281. doi: 10.1111/j.1440-1746.1997.tb00421.x. [DOI] [PubMed] [Google Scholar]
  4. Elba S., Giannuzzi V., Misciagna G., Manghisi O. G. Randomized controlled trial of tamoxifen versus placebo in inoperable hepatocellular carcinoma. Ital J Gastroenterol. 1994 Mar;26(2):66–68. [PubMed] [Google Scholar]
  5. Engstrom P. F., Levin B., Moertel C. G., Schutt A. A phase II trial of tamoxifen in hepatocellular carcinoma. Cancer. 1990 Jun 15;65(12):2641–2643. doi: 10.1002/1097-0142(19900615)65:12<2641::aid-cncr2820651207>3.0.co;2-r. [DOI] [PubMed] [Google Scholar]
  6. Farinati F., Salvagnini M., de Maria N., Fornasiero A., Chiaramonte M., Rossaro L., Naccarato R. Unresectable hepatocellular carcinoma: a prospective controlled trial with tamoxifen. J Hepatol. 1990 Nov;11(3):297–301. doi: 10.1016/0168-8278(90)90211-9. [DOI] [PubMed] [Google Scholar]
  7. Fuqua S. A., Fitzgerald S. D., Chamness G. C., Tandon A. K., McDonnell D. P., Nawaz Z., O'Malley B. W., McGuire W. L. Variant human breast tumor estrogen receptor with constitutive transcriptional activity. Cancer Res. 1991 Jan 1;51(1):105–109. [PubMed] [Google Scholar]
  8. Martínez Cerezo F. J., Tomás A., Donoso L., Enríquez J., Guarner C., Balanzó J., Martínez Nogueras A., Vilardell F. Controlled trial of tamoxifen in patients with advanced hepatocellular carcinoma. J Hepatol. 1994 Jun;20(6):702–706. doi: 10.1016/s0168-8278(05)80138-2. [DOI] [PubMed] [Google Scholar]
  9. Mazzaferro V., Regalia E., Doci R., Andreola S., Pulvirenti A., Bozzetti F., Montalto F., Ammatuna M., Morabito A., Gennari L. Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis. N Engl J Med. 1996 Mar 14;334(11):693–699. doi: 10.1056/NEJM199603143341104. [DOI] [PubMed] [Google Scholar]
  10. Simonetti R. G., Liberati A., Angiolini C., Pagliaro L. Treatment of hepatocellular carcinoma: a systematic review of randomized controlled trials. Ann Oncol. 1997 Feb;8(2):117–136. doi: 10.1023/a:1008285123736. [DOI] [PubMed] [Google Scholar]
  11. Vilana R., Bruix J., Bru C., Ayuso C., Solé M., Rodés J. Tumor size determines the efficacy of percutaneous ethanol injection for the treatment of small hepatocellular carcinoma. Hepatology. 1992 Aug;16(2):353–357. doi: 10.1002/hep.1840160212. [DOI] [PubMed] [Google Scholar]
  12. Villa E., Baldini G. M., Pasquinelli C., Melegari M., Cariani E., Di Chirico G., Manenti F. Risk factors for hepatocellular carcinoma in Italy. Male sex, hepatitis B virus, non-A non-B infection, and alcohol. Cancer. 1988 Aug 1;62(3):611–615. doi: 10.1002/1097-0142(19880801)62:3<611::aid-cncr2820620328>3.0.co;2-0. [DOI] [PubMed] [Google Scholar]
  13. Villa E., Camellini L., Dugani A., Buttafoco P., Grottola A., Manenti F. Variant liver estrogen and response to tamoxifen. Gastroenterology. 1996 Jul;111(1):271–272. doi: 10.1053/gast.1996.v111.agast961110271b. [DOI] [PubMed] [Google Scholar]
  14. Villa E., Camellini L., Dugani A., Zucchi F., Grottola A., Merighi A., Buttafoco P., Losi L., Manenti F. Variant estrogen receptor messenger RNA species detected in human primary hepatocellular carcinoma. Cancer Res. 1995 Feb 1;55(3):498–500. [PubMed] [Google Scholar]
  15. Villa E., Dugani A., Fantoni E., Camellini L., Buttafoco P., Grottola A., Pompei G., De Santis M., Ferrari A., Manenti F. Type of estrogen receptor determines response to antiestrogen therapy. Cancer Res. 1996 Sep 1;56(17):3883–3885. [PubMed] [Google Scholar]
  16. Villa E., Dugani A., Moles A., Camellini L., Grottola A., Buttafoco P., Merighi A., Ferretti I., Esposito P., Miglioli L. Variant liver estrogen receptor transcripts already occur at an early stage of chronic liver disease. Hepatology. 1998 Apr;27(4):983–988. doi: 10.1002/hep.510270413. [DOI] [PubMed] [Google Scholar]
  17. Zaman S. N., Melia W. M., Johnson R. D., Portmann B. C., Johnson P. J., Williams R. Risk factors in development of hepatocellular carcinoma in cirrhosis: prospective study of 613 patients. Lancet. 1985 Jun 15;1(8442):1357–1360. doi: 10.1016/s0140-6736(85)91785-4. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES