Skip to main content
Log in

Androgen Receptor-Blocking Agents

Potential Role in Pancreatic Cancer

  • Leading Article
  • Published:
Drugs & Aging Aims and scope Submit manuscript

Abstract

The growth of pancreatic adenocarcinoma may be under the control of the sex steroid hormone testosterone, besides other unknown stimuli. This premise was based on the discovery of androgen receptors, together with the enzymes aromatase and 5α-reductase, which use testosterone as a substrate, in malignant tissue. The additional support of low circulating serum testosterone and its stimulatory role in an animal model using human tumour xenografts further enhance this suggestion.

Confirmatory evidence has now come from a double-blind, placebo-controlled trial in patients with pancreatic cancer in which flutamide, the pure androgen receptor blocker, doubled survival duration over control patients. Flutamide was administered in a dosage of 250mg 3 times daily. Support for this finding has recently been presented at a meeting of the Pancreatic Society of Great Britain.

It is now important for further confirmatory studies to be carried out and to use flutamide in combination with other current adjuvant therapies in patients with pancreatic cancer.

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.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Rosewicz S, Wiedenmann B. Pancreatic carcinoma. Lancet 1997; 349: 485–9

    Article  PubMed  CAS  Google Scholar 

  2. Corbishley TP, Iqbal MJ, Wilkinson NIL, et al. Androgen receptor in human normal and malignant pancreatic tissue and cell lines. Cancer 1986; 57: 1992–5

    Article  PubMed  CAS  Google Scholar 

  3. Iqbal MJ, Greenway BA, Wilkinson NIL, et al. Sex steroid enzymes, aromatase and 5 alpha-reductase in the pancreas: a comparison of normal adult, foetal and malignant tissue. Clin Sci 1983; 65: 71–5

    PubMed  CAS  Google Scholar 

  4. Greenway BA, Iqbal MJ, Johnson PJ, et al. Low serum testosterone concentrations in patients with carcinoma of the pancreas. BMJ 1983; 286: 93–5

    Article  PubMed  CAS  Google Scholar 

  5. Greenway BA, Duke D, Pyin B, et al. The control of human pancreatic adenocarcinoma xenografts in nude mice by hormone therapy. Br J Surg 1982; 69: 595–7

    Article  PubMed  CAS  Google Scholar 

  6. Redding TW, Schally AV. Inhibition of growth of pancreatic carcinomas in animal models by hypothalamic hormones. Proc Natl Acad Sci U S A 1984; 81: 248–52

    Article  PubMed  CAS  Google Scholar 

  7. Gonzalez-Barcena D, Ibarra-Olmos MA, Garcia-Carrasco F, et al. Influence of D-Trp-6-LH-RH on the survival time in patients with advanced pancreatic cancer. Biomed Pharmacother 1989; 43: 313–7

    Article  PubMed  CAS  Google Scholar 

  8. Neumann F, Topert M. Pharmacology of antiandrogens. J Steroid Biochem 1986; 25: 885–95

    Article  PubMed  CAS  Google Scholar 

  9. Keating JJ, Johnson PJ, Cochrane AM, et al. Prospective randomized controlled trial of tamoxifen and cyproterone acetate in pancreatic carcinoma. Br J Cancer 1989; 60: 789–92

    Article  PubMed  CAS  Google Scholar 

  10. Swarovsky B, Wolf M, Havemann K, et al. Tamoxifen or cyproterone acetate in combination with buserelin are ineffective in patients with pancreatic adenocarcinoma. Oncology 1993; 50: 226–9

    Article  PubMed  CAS  Google Scholar 

  11. Poyet P, Labrie F, Comparison of the antiandrogenic/androgenic activities of flutamide, cyproterone acetate and magistral acetate. Mol Cell Endocrinol 1985; 42: 283–8

    Article  PubMed  CAS  Google Scholar 

  12. Imai K, Watanabe K, Takahashi O, et al. A study of the androgenic activity of antiandrogen [in Japanese]. Nippon Naibunpi Gakkai Zasshi 1990; 66: 597–606

    PubMed  CAS  Google Scholar 

  13. Greenway BA. Effect of flutamide on survival in patients with pancreatic cancer: results of a prospective, randomized, double-blind, placebo-controlled trial. BMJ (Clin Res Ed) 1998; 316: 1935–8

    Article  CAS  Google Scholar 

  14. Sharma JJ, Razvillas B, Stephens CD, et al. Phase II study of flutamide as second line chemotherapy in patients with advanced pancreatic cancer. Invest New Drugs 1997; 15: 361–4

    Article  PubMed  CAS  Google Scholar 

  15. de Takats P, Shaw J. Role of flutamide in the treatment of advanced pancreatic cancer [poster presentation]. 4th Annual Scientific Meeting of the Pancreatic Society of Great Britain and Ireland. Royal College of Physicians of London. Nov 1999, London

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Greenway, B.A. Androgen Receptor-Blocking Agents. Drugs & Aging 17, 161–163 (2000). https://doi.org/10.2165/00002512-200017030-00001

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00002512-200017030-00001

Keywords

Navigation