Advertisement

The Endocrinological Basis for Hormonal Therapy of Prostate Tumours

  • M. Motta
Conference paper
Part of the ESO Monographs book series (ESO MONOGRAPHS)

Abstract

The growth and the activity of the normal prostate is largely dependent upon androgens, a characteristic that is frequently retained (80% of all cases of prostatic cancer) by the prostatic cells which develop into neoplastic cells (either benign: benign prostatic hypertrophy, BPH, or malignant: prostatic carcinoma). This concept is supported by the fact that the lack of testicular function (either due to castration or to hypopituitarism prior to the age of 40) prevents the occurrence of prostatic tumours in males over 55 years of age. It has been reported that the members of a Russian sect who undergo ritual castration before the age of 35 never exhibit the symptoms of BPH and have a prostate smaller than normal (see [1] for review).

Keywords

Growth Hormone Adrenal Androgen Cyproterone Acetate LHRH Agonist Prostatic Growth 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Geller J and Vik Franson A: Endocrine dependent prostate disease. In: Serb M (ed) Perspectives in Andrology. Raven Press, New York 1989 Vol 53 pp 57–69Google Scholar
  2. 2.
    Huggins C, Stevens RE Jr and Hodges CV: Studies on prostatic cancer. II. The effects of castration on advanced carcinoma of the prostate gland. Arch Surg 1941 (43):209–223CrossRefGoogle Scholar
  3. 3.
    Vermeulen A: The androgens. In: Grey CH and James VHT (eds) Hormones in Blood. Academic Press, London 1979 Vol 3 pp 355–416Google Scholar
  4. 4.
    Piva F, Motta M and Martini L: Regulation of hypothalamic and pituitary function: long, short, and ultrashort feedback bops. In: DeGroot LJ (ed) Endocrinology. Grume and Stratton, New York 1979 pp 21–33Google Scholar
  5. 5.
    Harper ME, Pike A, Peeling WB and Griffiths K: Steroids of adrenal origin metabolised by human prostatic tissue in vivo and in vitro. J Endocrinol 1974(60):117–125PubMedCrossRefGoogle Scholar
  6. 6.
    Labrie F, Dupont A and Belanger A: Complete androgen blockade for the treatment of prostate cancer. In: De Vita VT, Hellman S and Rosenberg SA (eds) Important Advances in Oncology. Lippincott, Philadelphia 1985 pp 193–217Google Scholar
  7. 7.
    Labrie F, Dupont A, Belanger A and St Arnaud R: Treatment of prostate cancer with gonadotropin-releasing hormone agonists. Endocr Rev 1986 (7):67–74PubMedCrossRefGoogle Scholar
  8. 8.
    Tullner WW: Hormonal factors in the adrenal-dependent growth of the rat ventral prostate. NCI Monogr 1963 (12):211–223Google Scholar
  9. 9.
    Oesterling JE, Epstein JI and Walsh PC: The viability of adrenal androgens to stimulate the adult human prostate: an autopsy evaluation of men with hypogonadotropic hypogonadism and panhypopituitarism. J Urol 1986 (136):1030–1034PubMedGoogle Scholar
  10. 10.
    Krieg M, Bartsh W, Janssen W and Voigt KD: A comparative study of binding metabolism and endogenous levels of androgens in normal hyperplastic and carcinomatous human prostate. J Steroid Biochem 1979 (11) : 615–624PubMedCrossRefGoogle Scholar
  11. 11.
    Bruchovsky N and Wilson JD: The conversion of testosterone to 5alpha-androstan-17beta-ol-3-one by rat prostate in vivo and in vitro. J Biol Chem 1968 (243):2012–2021PubMedGoogle Scholar
  12. 12.
    Motta M, Zoppi S, Brodie AM and Martini L: Effect of 1,4,6-androstantriene-3,17-dione (ATD),4-hydroxy-4-androstene-3,17-dione (4-OH-A) and 4-acetoxy-4-androstene-3,17-dione (4-Ac-A) on the 5alpha-reduction of androgens in the rat prostate. J Steroid Biochem 1986 (25):593–599PubMedCrossRefGoogle Scholar
  13. 13.
    Brooks JR, Baptista EM, Berman C, Ham EA, Hichens M, Johnston DBR, Primka RL, Rasmusson GH, Reynolds GF, Schmitt SM and Arth GE: Response of rat ventral prostate to a new and novel 5alpha-reductase inhibitor. Endocrinology 1981 (109):830–836PubMedCrossRefGoogle Scholar
  14. 14.
    Blohm TR, Laughlin ME and Benson HD: Pharmacological induction of 5alpha-reductase deficiency in the rat: separation of testosterone-mediated and 5alpha-dihydrotestosterone-mediated effects. Endocrinology 1986 (119):959–966PubMedCrossRefGoogle Scholar
  15. 15.
    Fang S and Liao S: Androgen receptors. Steroid-and-tissue specific retention of 17beta-hydroxy-5alpha-androstan-3-one-protein complex by the cell nuclei of ventral prostate. J Biol Chem 1971 (246):16–24PubMedGoogle Scholar
  16. 16.
    Barrack ER and Coffey DS: The specific binding of estrogens and androgens to the nuclear matrix of sex hormone responsive tissues. J Biol Chem 1980 (255):7265–7275PubMedGoogle Scholar
  17. 17.
    Isaacs JT, Brendler CB and Walsh PC: Changes in the metabolism of dihydrotestosterone in the hyperplastic human prostate. J Clin Endocrinol Metab 1983 (56):139–146PubMedCrossRefGoogle Scholar
  18. 18.
    Geller J: Benign prostatic hypertrophy: current understanding of its pathogenesis. In: Labrie F and Proulx L (eds) Endocrinology. Excerpta Medica, Amsterdam 1984 pp 909–912Google Scholar
  19. 19.
    Smith CB, Masters JRW and Ghamadian R: Differential androgen metabolism in prostatic tumors. J Endocr 1980 (85):5–6Google Scholar
  20. 20.
    Kirdani RY, Emrich LJ, Pontes EJ, Priore RL and Murphy GP: A comparison of estrogen and androgen receptor levels in human prostatic tissue from patients with non-metastatic and metastatic carcinoma and benign prostatic hyperplasia. J Steroid Biochem 1985 (22):569–575PubMedCrossRefGoogle Scholar
  21. 21.
    Thompson SA, Rowley DR and Heidger PM: Effects of estrogen upon the fine structure of epithelium and stroma in the rat ventral prostate gland. Invest Urol 1979 (17):83–89PubMedGoogle Scholar
  22. 22.
    Mawhinney MG and Neubauer BL: Actions of estrogen in the male. Invest Urol 1979 (16):409–420PubMedGoogle Scholar
  23. 23.
    Krieg M, Bartsch W, Thomsen M and Voigt KD: Androgens and estrogens: their interaction with stroma and epithelium of human benign hyperplasia and normal prostate. J Steroid Biochem 1983 (19):155–161PubMedCrossRefGoogle Scholar
  24. 24.
    Ghanadian R and Puah CM: Relationship between oestradiol-17beta, testosterone, dihydrotestosterone and 5alpha-androstane-3alpha, 17beta-diol in human benign hypertrophy and carcinoma of the prostate. J Endocr 1981 (88):255–262PubMedCrossRefGoogle Scholar
  25. 25.
    Stone NN, Fair WR and Fishman J: Estrogen formation in human prostatic tissue from patients with and without benign prostatic hyperplasia. Prostate 1986 (9):311–318PubMedCrossRefGoogle Scholar
  26. 26.
    Kaburagi Y, Marino MB, Kirdani RY, Greco JP, Karr JP and Sandberg AA: The possibility of aromatizaron of androgen in human prostate. J Steroid Biochem 1987 (26):739–742PubMedCrossRefGoogle Scholar
  27. 27.
    Thorner MO: Prolactin: clinical physiology and the significance and management of hyperprolactinemia. In: Martini L and Besser GM (eds) Clinical Neuroendocrinology. Academic Press, New York 1977 pp 319–361Google Scholar
  28. 28.
    Jacobi GH and Wenderoth UK: New forms and future perspectives in endocrine treatment of prostatic carcinoma. Progress and Controversies in Oncological Urology. Springer, Berlin 1980Google Scholar
  29. 29.
    Aragona C, Bohnet HG and Friesen HG: Localization of prolactin binding in prostate and testis: the role of serum prolactin concentration on the testicular LH receptor. Acta Endocrin 1977 (84):402–408Google Scholar
  30. 30.
    Jacobi GH: Palliativtherapie des Prostatakarzinoms. Endokrinologische Grundlagen, Klinische Situation, Prolaktinin neues Prinzip. Zuckschwerdt, München 1980Google Scholar
  31. 31.
    Smith C, Assimos D, Lee C and Grayhack JT: Metabolic action of prolactin on the prostate: independent of androgen action. Prostate 1985 (6):49PubMedCrossRefGoogle Scholar
  32. 32.
    Boyns AR, Griffiths K, Pierrepoint CG and Peeling WB: Prolactin and the prostate. In: Goland M (ed) Normal and Abnormal Growth of the Prostate. Charles C Thomas, Springfield 1975 pp 431–444Google Scholar
  33. 33.
    Manandhar SF and Thomas JA: Effect of prolactin on the metabolism of androgen by the rat ventral prostate gland in vitro. Invest Urol 1976 (14):20–22PubMedGoogle Scholar
  34. 34.
    Farnsworth WE, Slannwhile WR Jr and Sharma M: Interaction of prolactin and testosterone in the human prostate. Urol Res 1977 (15):83–91Google Scholar
  35. 35.
    Berelowitz M, Szabo M, Frohman LA, Firestone S and Chu L: Somatomedin-C mediates growth hormone negative feedback by effects on both the hypothalamus and the pituitary. Science 1981 (212):1279–1281PubMedCrossRefGoogle Scholar
  36. 36.
    Lostroh AJ and Li CH: Stimulation of sex accessories of hypophysectomised male rat by non-gonadotrophin hormone of the pituitary gland. Acta Endocrin 1975 (25):1–16Google Scholar
  37. 37.
    British Prostate Study Group: Evaluation of plasma hormone concentrations in relation to clinical staging in patients with prostatic cancer. Br J Urol 1979 (51):382–389CrossRefGoogle Scholar
  38. 38.
    Sibley PEC, Harper ME, Peeling WB and Griffiths K: Growth hormonal and prostatic tumors: localization using a monoclonal human growth hormone antibody. J Endocr 1984 (103):311–315PubMedCrossRefGoogle Scholar
  39. 39.
    Wilson EM and Smith EP: Growth factors in the prostate. Prog Clin Biol Res 1987 (239):205–233PubMedGoogle Scholar
  40. 40.
    James R and Bradshaw RA: Polypeptide growth factors. Ann Rev Biochem 1984 (53):259–292PubMedCrossRefGoogle Scholar
  41. 41.
    Moses HL, Tucker RF, Leof EB, Coffey JR Halber J and Shipley GD: Type beta transforming growth factor is a growth stimulator and a growth inhibitor. In: Feramisco J, Ozanne B and Stiles C (eds) Cancer Cells. Cold Spring Harbor Laboratory, Cold Spring Harbor 1985 Vol 3 pp 65–74Google Scholar
  42. 42.
    Roberts AB, Anzano MA, Wakefield LM, Roche NS, Stern DF and Sporn MB: Type beta transforming growth factor: a bifunctional regulator of cellular growth. Proc Natl Acad Sci Usa 1985 (82):119–123PubMedCrossRefGoogle Scholar
  43. 43.
    Nishi N, Matuo Y, Muguruma Y, Yoshitake Y, Nishikawa K and Wada F: A human prostatic growth factor (hPGF): partial purification and characterization. Biochem Biophys Res Commun 1985 (132):1103–1109PubMedCrossRefGoogle Scholar
  44. 44.
    Story MT, Esch F, Shimasaki S, Sasse J, Jacobs SC and Lawson RK: Amino-Terminal sequence of a large form of basic fibroblast growth factor isolated from human benign prostatic hyperplastic tissue. Biochem Biophys Res Commun 1987 (142):702–709PubMedCrossRefGoogle Scholar
  45. 45.
    Jinno H, Ueda K, Otaguro K, Kato T, Ito J and Tanaka R: Prostate growth factor in the extracts of benign prostatic hypertrophy. Eur Urol 1986 (12):41–48PubMedGoogle Scholar
  46. 46.
    Nishi N, Matuo Y and Wada F: Partial purification of a major type of rat prostatic growth factor: characterization as an epidermal growth factor-related mitogen. Prostate 1988 (13):209–220PubMedCrossRefGoogle Scholar
  47. 47.
    Mydlo JH, Bulbul MA, Richon VM, Heston WDW and Fair W: Heparin-binding growth factor isolated from human prostatic extracts. Prostate 1988 (12):343–355PubMedCrossRefGoogle Scholar
  48. 48.
    Crabb JW, Armes LG, Johnson CM and McKeehan WL: Characterization of multiple forms of prostatropin (prostate epithelial growth factor) from bovine brain. Biochem Biophys Res Commun 1986 (136):1155–1161PubMedCrossRefGoogle Scholar
  49. 49.
    Maddy SQ, Chisholm GD, Hawkins RA and Habib FK: Localization of epidermal growth factor receptors in the human prostate by biochemical and immunocytochemical methods. J Endocr 1987 (113):147–153PubMedCrossRefGoogle Scholar
  50. 50.
    Matuo Y, Nishi N, Matsui S, Sandberg AA, Isaacs JT and Wada F: Heparin binding affinity of rat prostatic growth factor in normal and cancerous prostates: partial purification and characterization of rat prostatic growth factor in the Dunning tumor. Cancer Research 1987 (47):188–192PubMedGoogle Scholar
  51. 51.
    Wilding G, Valverius E, Knabbe C and Gelmann EP: Role of transforming growth factor-alpha in human prostate cancer cell growth. Prostate 1989 (15):1–2PubMedCrossRefGoogle Scholar
  52. 52.
    Davies P and Eaton CL: Binding of epidermal growth factor by human normal hypertrophic and carcinomatous prostate. Prostate 1989 (14):123–132PubMedCrossRefGoogle Scholar
  53. 53.
    Nishi N, Matuo Y, Kunitomi K, Takenaka I, Usami M, Kotake T and Wada F: Comparative analysis of growth factors in normal and pathologic human prostates. Prostate 1988 (13):39–48PubMedCrossRefGoogle Scholar
  54. 54.
    Peehl DM, Wong ST, Bazinet M and Stamey TA: In vitro studies of human prostatic epithelial cells: attempts to identify distinguishing features of malignant cells. Growth Factors 1989 (1):237–250PubMedCrossRefGoogle Scholar
  55. 55.
    McKeehan WL, Adams PS and Rosser MP: Direct mitogenic effects of insulin, epidermal growth factor, glucocorticoid, cholera toxin, unknown pituitary factors and possibly prolactin, but not androgen on normal rat prostate epithelial cells in serum-free primary cell culture. Cancer Res 1984 (44):1998–2010PubMedGoogle Scholar
  56. 56.
    Fowler JE, Lau JLT, Ghosh L, Mills SE and Mounzer A: Epidermal growth factor and prostatic carcinoma: an immunohistochemical study. J Urol 1988 (139):857–861PubMedGoogle Scholar
  57. 57.
    Traish AM and Wotiz HM: Prostatic epidermal growth factors receptors and their regulation by androgens. Endocrinology 1987 (121):1461–1467PubMedCrossRefGoogle Scholar
  58. 58.
    Kirdani RY, Muntzing J, Varkarakis JM, Murphy GP and Sandberg AA: Studies on the antiprostatic action of estracyt, a nitrogen mustard of estradiol. Cancer Res 1974 (34):1031–1037PubMedGoogle Scholar
  59. 59.
    Hoisaeter PA: Incorporation of 3H-thymidine into rat ventral prostate in organ culture. Invest Urol 1975 (12):479–483PubMedGoogle Scholar
  60. 60.
    Daehlin L: On the effects of oestrogen in the male. Some effects of different oestrogenic substances in rats and men with prostatic carcinoma. Scand J Urol Nephrol 1985 (91 Suppl):21–35Google Scholar
  61. 61.
    Tan SY, Antonipillai I and Murphy BEP: Inhibition of testosterone metabolism in the human prostate. J Clin Endocrinol Metab 1984 (39):936–941CrossRefGoogle Scholar
  62. 62.
    Massa R and Martini L: Interference with the Salpha-reductase system. Gynec Invest 1972 (2):253–270CrossRefGoogle Scholar
  63. 63.
    Jagarinec N and Givner ML: Inhibition of testosterone metabolism of medrogestone in rat ventral prostate in vivo and in vitro. Arch Androl 1981 (7):39–44PubMedCrossRefGoogle Scholar
  64. 64.
    Martini L and Motta M (eds) Androgens and Antiandrogens. Raven Press, New York 1977Google Scholar
  65. 65.
    Neumann F: Pharmacology and clinical uses of cyproterone acetate. In: Furr BJA and Wakeling AE (eds) Pharmacology and Clinical Uses of Inhibitors of Hormone Secretion and Action. Bailliere Tindall, London 1987 pp 132–159Google Scholar
  66. 66.
    Neri R and Kassen N: Pharmacology and clinical uses of flutamide. In: Furr BJA and Wakeling AE (eds) Pharmacology and Clinical Uses of inhibitors of Hormone Secretion and Action. Bailliere Tindal, London 1987 pp 160–169Google Scholar
  67. 67.
    Raynaud JP, Bonne C, Moguilewsky M, Levebvre FA, Belanger A and Labrie F: The pure antiandrogen RH 23908 (anandron), a candidate of choice for the combined antihormonal treatment of prostatic cancer: a review. Prostate 1984 (5):299–324PubMedCrossRefGoogle Scholar
  68. 68.
    Neumann F, Habenicht UF and Schacher A: Antiandrogens and target cell response. Different in vivo effects of cyproterone acetate, flutamide and cyproterone. In: McKerns KW, Aakvaag A and Hansson V (eds) Regulation of Target Cell Responsiveness. Plenum Press, New York 1984 Vol 2 pp 489–527Google Scholar
  69. 69.
    Furr BJA: Pharmacological properties and potential clinical utility of ICI 176,334: a novel, non-steroidal, peripherally selective antiandrogen. In: Motta M and Serio M (eds) Hormonal therapy of Prostatic Diseases: Basic and Clinical Aspects. Medicom, Amsterdam 1988 pp 148–161Google Scholar
  70. 70.
    Denis L: A new non-steroidal anti-androgen. In: Murthy JP and Khourys (eds) Therapeutic Progress in Urological Cancers. Alan R Liss Inc. New York 1989 pp 95–103Google Scholar
  71. 71.
    Zoppi S, Cocconi M, Natali A, Costantini A, Serio M, Martini L and Motta M: In vitro effects of an aromatase inhibitor of 5alpha-reductase activity in human hypertrophic prostatic tissue. J Clin Endocrinol Metab 1986 (63):269–271PubMedCrossRefGoogle Scholar
  72. 72.
    Rasmusson GH: Biochemistry and pharmacology of 5alpha-reductase inhibitors. In: Furr BJA and Wakeling AE (eds) Pharmacology and Clinical Uses of Inhibitors of Hormone Secretion and Action. Bailliere Tindall, London 1987 pp 308–325Google Scholar
  73. 73.
    Wenderoth UK, George FW and Wilson JD: The effect of a Salpha-reductase inhibitor on androgen-mediated growth of the dog prostate. Endocrinology 1983 (113):569–573PubMedCrossRefGoogle Scholar
  74. 74.
    Rittmaster RS, Stoner E, Thompson DL, Nance D and Lasseter KC: Effect of MK-906, a specific 5alpha-reductase inhibitor, on serum androgens and androgen conjugates in normal men. J Androl 1989 (10):259–262PubMedGoogle Scholar
  75. 75.
    Habenicht UF, Scwartz K, Schweikert HU, Neumann F and El Etreby MF: Development of a model for the induction of estrogen-related prostatic hyperplasia in the dog and its response to the aromatase inhibitor 4-hydroxy-4-androstene-3,17-dione: preliminary results. Prostate 1986 (8):181–194PubMedCrossRefGoogle Scholar
  76. 76.
    Baba Y, Matsuo M and Schally AV: Structure of the porcine LH-and FSH-releasing hormone. II. Confirmation of the proposed structure by conventional sequential analyses. Biochem Biophys Res Commun 1971 (44):459–461PubMedCrossRefGoogle Scholar
  77. 77.
    Karten MJ and Rivier JE: Gonadotropin-releasing hormone analog design. Strucure-function studies toward the development of agonists and antagonists: rationale and perspective. Endocr Rev 1986 (7):44–66PubMedCrossRefGoogle Scholar
  78. 78.
    Bhasin S and Swerdloff RS: Mechanisms of gonadotropin-releasing hormone agonist action in the human male. Endocr Rev 1986 (7):106–114PubMedCrossRefGoogle Scholar
  79. 79.
    Schally AV, Comaru-Schally AM and Redding TW: Antitumor effects of analogs of hypothalamic hormones in endocrine-dependent cancers. Proc Soc Exp Biol Med 1984 (175):259–281PubMedGoogle Scholar
  80. 80.
    Clayton RN and Catt KJ: Gonadotropin-releasing hormone receptors: characterization, physiological regulation and relationship to reproductive function. Endocr Rev 1981 (2):186–201PubMedCrossRefGoogle Scholar
  81. 81.
    Fekete M, Redding TW, Comaru-Schally AM, Pontes JD, Connelly RW, Srkalovic G and Schally AV: Receptors for luteinizing hormone-releasing hormone, somatostatin, prolactin and epidermal growth factor in rat and human prostate cancers and in benign prostate hyperplasia. Prostate 1989 (14):191–208PubMedCrossRefGoogle Scholar
  82. 82.
    Klign JGM, De Voogt HJ, Schroder FH and De Jong FH: Combined treatment with buserelin and cyproterone acetate in metastatic prostatic carcinoma. Lancet 1985 (2):493PubMedCrossRefGoogle Scholar
  83. 83.
    Huhtaniemi I, Nikula H and Rannikko S: Treatment of prostatic cancer with a gonadotropin-releasing hormone agonist analog: acute and long term effects on endocrine functions of testis tissue. J Clin Endocrinol Metab 1985 (61):698–704PubMedCrossRefGoogle Scholar
  84. 84.
    Bouffioux C, Denis L, Mahler C and deLeval J: Le traitement du cancer avancé de la prostate au moyen des analogues de la LHRH: comment prévenir la flambee tumorale (flare-up) initiale possible? Acta Urol Belg 1986 (54):304–308PubMedGoogle Scholar
  85. 85.
    Redding TW, Coy DH and Schally AV: Prostate carcinoma tumor size in rats decreases after administration of antagonists of luteinizing hormone-releasing hormone. Proc Natl Acad Sci USA 1982 (79):1273–1276PubMedCrossRefGoogle Scholar
  86. 86.
    Hierowski MT, Altamirano P, Redding TW and Schally AV: The presence of LHRH-like receptors in Dunning R-3327 H prostate tumors. Febs Lett 1983 (154):92–96PubMedCrossRefGoogle Scholar
  87. 87.
    Forti G, Salerno R, Moneti G, Zoppi S, Fiorelli G, Marinoni T, Natali A, Costantini A, Serio M, Martini L and Motta M: Three-month treatment with a long acting gonadotropin-releasing hormone agonist of patients with benign prostatic hyperplasia: effects on tissue androgen concentration, 5alpha-reductase activity and androgen receptor content. J Clin Endocrinol Metab 1989 (68):461–468PubMedCrossRefGoogle Scholar
  88. 88.
    Geller J, Albert JD, Nachsheim DA and Loza D: Comparison of prostatic cancer tissue dihydrotestosterone levels at the time of relapse following orchiectomy or estrogen therapy. J Urol 1984 (132):693–696PubMedGoogle Scholar
  89. 89.
    Trachtenberg J: Optimal testosterone concentration for the treatment of prostatic cancer. J Urol 1985 (133):888–892PubMedGoogle Scholar
  90. 90.
    Worgul TJ, Santen RJ, Samojlik E, Veldhuis JD, Lipton A, Harvey HA, Drago JR and Rohner TJ: Clinical and biochemical effect of aminoglutethimide in the treatment of advanced prostatic carcinoma. J Urol 1983 (129):51–57PubMedGoogle Scholar
  91. 91.
    Sonino N: The endocrine effects of ketoconazole. J Endocrinol Invest 1986:341–347Google Scholar
  92. 92.
    Kuhn JM, Billebaud T, Navratil H, Moulonguet A et al: Prevention of the transient adverse effects of a gonadotropin-releasing hormone analogue (buserelin) in metastatic prostatic carcinoma by administration of an antiandrogen (nilutamide). N Engl Med 1989 (321):413–418CrossRefGoogle Scholar
  93. 93.
    Ahmann FR and Schifman RB: Prospective comparison between serum monoclonal prostate specific antigen and acid phosphatase measurements in metastatic prostatic cancer. J Urol 1987 (137):431–434PubMedGoogle Scholar
  94. 94.
    Navratil H: Double-blind study of anandron versus placebo in stage D2 prostate cancer patients receiving buserelin: results on 49 cases from a multicentre study. In: Murphy GP, Khoury S, Kuss R, Chatelain C and Denis L (eds) Prostate Cancer. Part A: Research, Endocrine Treatment and Histopathology. Progress in Clinical and Biological Research. Vol 243. Alan R Liss, New York 1987 pp 401–410Google Scholar
  95. 95.
    Labrie F, Dupont A, Cusan L, Giguere M et al:Combination therapy with flutamide and castration (LHRH agonist or orchiectomy) in previously untreated patients with clinical stage D2 prostate cancer: Today’s therapy of choice. J Steroid Biochem 1988 (30):107–111PubMedCrossRefGoogle Scholar
  96. 96.
    Crawford ED, Eisenberger MA, Mcleod DG, Spaulding JT et al: A controlled trial of leuprolide with and without flutamide in prostatic carcinoma. N Engl J Med 1989 (321):419–424PubMedCrossRefGoogle Scholar
  97. 97.
    Schroeder FH, Lock TMTW, Chada DR, Debruyne FMJ et al: Metastatic cancer of the prostate managed with buserelin, versus buserelin plus cyproterone acetate. J Urol 1987 (137):912–917PubMedGoogle Scholar
  98. 98.
    Eighth Congress of the European Association of Urology. London, 18–21 May 1988, Abstracts 42–44Google Scholar
  99. 99.
    Serb M, Costantini A and Di Silverio F: Use of LHRH analogue ‘Zoladex’ depot alone and with cyproterone acetate in the treatment of advanced prostatic carcinoma. VIII Int Symposium on Future Trends in Chemotherapy, 28–30 March 1988, Tirrenia (Pisa), p 179 (Abstract)Google Scholar
  100. 100.
    Raynaud JP, Namer M and Ojasoo p (eds): Am J Clin Oncol 1988 (11 ) suppl 2Google Scholar
  101. 101.
    Moreau JP and De Fendis FV: Pharmacological studies of somatostatin and somatostatin-analpgues: therapeutic advance and perspectives. Life Sci 1987 (40):419–437PubMedCrossRefGoogle Scholar
  102. 102.
    Defeudis FV and Moreau JP: Studies on somatostatin analogues might lead to new therapies for certain types of cancer. TIPS 1986 (10):384–386Google Scholar
  103. 103.
    Schally AV and Redding TW: Somatostatin anabgs as adjuncts to agonists of luteinizing hormone-releasing hormone in the treatment of experimental prostate cancer. Proc Natl Acad Sci Usa 1987 (84):7275–7279PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1991

Authors and Affiliations

  • M. Motta
    • 1
  1. 1.Department of EndocrinologyUniversity of MilanoMilanoItaly

Personalised recommendations