Clinical Trials of the LH-RH Analogue Leuprolide in Human Breast Cancer

  • H. A. Harvey
  • A. Lipton
  • D. T. Max
Conference paper

Abstract

Leuprolide (D-leu6-Des Gly10-Pro9-NH Et-LH-RH) is a potent analogue of the hypothalamic human gonadotropin-releasing hormone (LH-RH). The function of the native hormone LH-RH is to cause episodic release of gonadotropins by the pituitary gland. The chronic administration of highly potent LH-RH analogues (superagonists) such as leuprolide, causes pituitary desensitization leading, paradoxically, to inhibition of LH and FSH and consequently, to decreased output of gonadal sex steroids (1–4). Effective tumor regression has been reported in female rats bearing the dimethyl-benz-anthrancene induced mammary carcinoma treated chronically with leuprolide [5]. Thus, these physiologic considerations and experimental data provided a scientific rationale for conducting clinical trials of leuprolide and other LH-RH agonists in human breast cancer.

Keywords

Toxicity Estrogen Cortisol Diarrhea Flare 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Schally AV (1978) Aspects of hypothalamic regulation of the pituitary gland. Its implications for the control of reproductive processes. Science 202: 18–28PubMedCrossRefGoogle Scholar
  2. 2.
    Maynard PV, Nicholson RI (1979) Effects of high doses of a series of new luteinizing hormone-releasing hormone analogues in intact female rats. Br J Cancer 39: 274–279PubMedCrossRefGoogle Scholar
  3. 3.
    Ying SY, Guillermin R (1979) (D-TRP)-Luteinizing-hormone-releasing factor inhibits follicular development in hypophysectomized rats. Nature 180: 593–595CrossRefGoogle Scholar
  4. 4.
    Rabin D, McNeil LW (1980) Pituitary and gonadal desensitization after continuous luteinizing hormone-releasing hormone infusion in normal females. J Clin Endocrinol Metab 51: 873–876PubMedCrossRefGoogle Scholar
  5. 5.
    Harvey HA, Lipton A, Max DT, Pearlman HG, Diaz-Perches R, de la Garza J (1985) Medical castration produced by the GnRH analogue leuprolide to treat metastatic breast cancer. J Clin Oncol 3: 1068–1072PubMedGoogle Scholar
  6. 6.
    Klijn JGM, de Jong FH, Blankenstein MA, et al. (1984) Antitumor and endocrine effects of chronic LH-RH agonist treatment ( Buserelin) with or without tamoxifen in premenopausal metastatic breast cancer. Breast Cancer Res Treat 4: 209–220PubMedCrossRefGoogle Scholar
  7. 7.
    Williams MR, Walker KJ, Turkes A, Blarney RW, Nicholson RI (1986)The use of an LH-RH agonist (ICI 118630, Zoladex) in advanced premenopausal breast cancer. Br J Cancer 53(5): 629–636PubMedCrossRefGoogle Scholar
  8. 8.
    Harvey HA, Lipton A, Max DT (1984) LH-RH analogs for human mammary carcinoma. In: Vickery BH, Nestor JJ, Jr., Hafez ESE (eds) LH-RH and its analogs — contraceptive and therapeutic applications. MTP Press, Lancaster-Boston, p 329Google Scholar
  9. 9.
    Eidne KA, Flanagan CA, Millar RP (1985) Gonadotropin-releasing hormone binding sites in human breast carcinoma. Science 229: 989–991PubMedCrossRefGoogle Scholar
  10. 10.
    Miller WR, Scott WN, Morris R, Fruser HM, Sharpe RM (1985) Growth of human breast cancer cells inhibited by luteinizing hormone releasing hormone agonist. Nature 313: 231–233PubMedCrossRefGoogle Scholar
  11. 11.
    Labrie F, Dupont A, Belanger A, Giguere M, Lacoursiere Y, Emond J, Monfette G, Bergeron V (1985) Combination therapy with flutamide and castration (LH-RH agonist or orchiectomy) in advanced prostate cancer: a marked improvement in response and survival. J Steroid Biochem 23 (5B): 833–841PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1988

Authors and Affiliations

  • H. A. Harvey
  • A. Lipton
  • D. T. Max

There are no affiliations available

Personalised recommendations