Flutamide and Other Antiandrogens in the Treatment of Advanced Prostatic Carcinoma

  • Pramod C. Sogani
  • Willet F. WhitmoreJr.
Part of the Cancer Treatment and Research book series (CTAR, volume 39)


Prostatic cancer is the second most common malignancy in males and the third leading cause of cancer deaths in men in the United States. It is estimated that in 1987 there were 96,000 newly diagnosed cases and 27,000 deaths from prostatic cancer in the United States [1] Approximately 50% of men with prostatic cancer have advanced disease at the time of initial presentation. The realistic objective of treatment in these patients is palliation rather than cure. In 1941, Huggins and Hodges reported the results of their pioneering work, revealing that castration or additive estrogen therapy produced regression of prostatic cancer [2,3]. Although the majority of patients with advanced prostatic cancer can be palliated by either of these hormonal manipulations, the treatments are not without drawbacks. For example, castration is an invasive procedure, psychologically unacceptable to some patients, and estrogen therapy may be associated with fluid retention, thromboembolic complications, gynecomastia, and gastrointestinal side effects. Therefore, an effective systemic therapy readily acceptable to all patients and without side effects remains a desirable goal. Antiandrogens are one of several approaches that have been explored as alternatives to castration or estrogens in patients with advanced prostatic cancer.


Prostatic Cancer Advanced Prostatic Cancer Estrogen Therapy Cyproterone Acetate LHRH Agonist 
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.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Silverberg E, Lubera J (1987): Cancer statistics, Cancer 37: 2–19.Google Scholar
  2. 2.
    Huggins C, Hodges CV (1941): Studies on prostate cancer I. The effects of castration, of estrogen and of androgen injection on serum phosphatases in metastatic carcinoma of the prostate. Cancer Res 1: 293–297.Google Scholar
  3. 3.
    Huggins C, Stevens RE, Hodges CV (1941): Studies on prostate cancer II. The effect of castration on clinical patients with carcinoma of the prostate. Arch Surg 43: 209–213.Google Scholar
  4. 4.
    Bruchovsky N, Wilson JO (1968): The conversion of testosterone to a 5-alpha-androstane-17-ß-ol-3-one by rat prostate in vivo and in vitro. J Biol Chem 243: 2012–2021.PubMedGoogle Scholar
  5. 5.
    Anderson KM, Liao S (1968): Selective retention of dihydrotestosterone by prostatic nuclei. Nature 219: 277–279.PubMedCrossRefGoogle Scholar
  6. 6.
    Walsh PC (1975): Physiologic basis for hormonal therpay in carcinoma of the prostate. Urol Clin North Am 2: 125–140.PubMedGoogle Scholar
  7. 7.
    Scott WW, Schirmer HKA (1966): A new oral progestational steroid effective in treating prostate cancer. Trans Am Assoc AU Surg 58: 54–60.Google Scholar
  8. 8.
    Wein AJ, Murphy JJ (1973): Experience in the treatment of prostatic carcinoma with cyproterone acetate. J Urol 109: 68–70.PubMedGoogle Scholar
  9. 9.
    Smith RB, Walsh PC, Goodwin WE (1973): Cyproterone acetate in the treatment of advanced carcinoma of the prostate. J Urol 110: 106–108.PubMedGoogle Scholar
  10. 10.
    Geller J, Vazakas G, Fruchtman B, et al (1968): The effect of cyproterone acetate on advanced carcinoma of the prostate. Surg Gynecol Obstet 127: 748–758.PubMedGoogle Scholar
  11. 11.
    Jacobi GH, Altwein JE, Kurtt KH, et al (1980): Treatment of advanced prostatic cancer with parenteral cyproterone acetate: a phase III randomized trial. Br J Urol 52: 208–215.PubMedCrossRefGoogle Scholar
  12. 12.
    Tveter KJ, Otnes B, Hannestad R (1978): Treatment of prostatic carcinoma with cyproterone acetate. Scand J Urol Nephrol 12: 115–118.PubMedCrossRefGoogle Scholar
  13. 13.
    Tveter KJ, Attramadal A, Hannested R, Otnes B (1979): Morphological study on the effect of cyproterone acetate on human prostatic carcinoma. Scand J Urol Nephrol 13: 237–243.PubMedCrossRefGoogle Scholar
  14. 14.
    Neri RO, Florance K, Koziol P, VanCleave S (1972): A biological profile of a non-steroidal antiandrogens SCH-13521 (4’nitro-3’-trifluorome-thylisdobutyranilde). Endocrinology 91: 427–437.PubMedCrossRefGoogle Scholar
  15. 15.
    Neri RO, Monahan M (1972): Effects of novel nonsteroidal antiandrogen on canine prostatic hyperplasia. Invest Urol 10: 123–130.PubMedGoogle Scholar
  16. 16.
    Peets E, Henson F, Neri R, Tabachnick I (1973): Effects of nonsteroidal antiandrogen SCH 13521 on testosterone disposition in rats. Fed Proc 32: 759.Google Scholar
  17. 17.
    Varkarakis MJ, Kirdani RY, Yamanaka H, et al (1975): Prostatic effect of a nonsteroidal antiandrogen. Invest Urol 12: 275–284.PubMedGoogle Scholar
  18. 18.
    Muntzing J, Varkarakis MJ, Yamanaka H, et al (1974): Proc Soc Exp Biol Med 146: 849–854.PubMedGoogle Scholar
  19. 19.
    Jacobo E, Schmidt JD, Weinstein SH, Flocks RH (1976): Comparison of flutamide (SCH 13521) and diethylstilbestrol in untreated advanced prostatic cancer. Urology 8: 231–233.PubMedCrossRefGoogle Scholar
  20. 20.
    Neri R, Kassem N (1984): Biological and clinical properties of antiandrogens. Prog Cancer Res Ther 31: 507–518.Google Scholar
  21. 21.
    Prout GR Jr, Irwin RL J, Khmer B, et al (1975): Prostatic cancer and SCH 13521: II. Histological alterations and the pituitary gonadal axis. J Urol 113: 834–840.PubMedGoogle Scholar
  22. 22.
    Hellman L, Bradlow HL, Freed S, et al (1977): The effect of flutamide on testosterone metabolism and the plasma levels of androgens and gonadotropins. J Clin Endocrinol Metab 45: 1224–1229.PubMedCrossRefGoogle Scholar
  23. 23.
    Fukushima DK, Levin J, Kream J, et al (1978): Effect of flutamide on Cortisol metabolism. J Clin Endocrinol Metab 47: 788–791.PubMedCrossRefGoogle Scholar
  24. 24.
    Knuth VA, Hano R, Nieschlag E (1984): J Clin Endocrinol Metab 59: 963–969.PubMedCrossRefGoogle Scholar
  25. 25.
    Irwin RJ, Prout GR Jr (1973): A new antiprostatic agent for treatment of prostatic carcinoma. Surg Forum 23: 536–537.Google Scholar
  26. 26.
    Sogani PC, Whitmore WF Jr (1979): Experience with flutamide in previously untreated patients with advanced prostatic cancer. J Urol 122: 640–643.PubMedGoogle Scholar
  27. 27.
    Sogani PC, Vagaiwalla M, Whitmore WF (1984): Experience with flutamide in patients with advanced prostatic cancer without prior endocrine therapy. Cancer 54: 744–750.PubMedCrossRefGoogle Scholar
  28. 28.
    Keating MA, Griffin PO, Schiff SF (1986): Flutamide in the treatment of advanced prostate cancer. J Urol 135: 203A.Google Scholar
  29. 29.
    Sogani PC, Ray B, Whitmore WF Jr (1975): Advanced prostatic carcinoma; flutamide therapy after conventional endocrine therapy. Urology 6: 164–166.PubMedCrossRefGoogle Scholar
  30. 30.
    Stolier BV, Albert DJ (1974): SCH 13521 in the treatment of advanced carcinoma of the prostate. J Urol 111: 803–807.Google Scholar
  31. 31.
    Narayana AS, Luening SA, Culp DA (1981): Flutamide in the treatment of metastatic carcinoma of the prostate. Br J Urol 53: 152–153.PubMedCrossRefGoogle Scholar
  32. 32.
    MacFarlane Jr, Tolley DA (1985): Flutamide therapy for advanced prostatic cancer: a Phase II study. Br J Urol 57: 172–174.PubMedCrossRefGoogle Scholar
  33. 33.
    Morse MJ, Whitmore WF Jr (1985): Clinical management of advanced prostatic cancer. In Hollander VP (ed): Hormonally Responsive Tumors. New York, Academic Press, pp 431–468.Google Scholar
  34. 34.
    Catalona WJ (1984): Endocrine Therapy in Prostate Cancer. New York, Grune Stratton, pp 145–171.Google Scholar
  35. 35.
    Johnson DE, Kaebler KE, Yala AG (1975): Megestrol acetate for treatment of advanced carcinoma of the prostate. J Surg Oncol 7: 9–15.PubMedCrossRefGoogle Scholar
  36. 36.
    Geller J, Albert J, Yen SS (1978): Treatment of advanced cancer of prostate with megestrol acetate. Urology 12: 537–541.PubMedCrossRefGoogle Scholar
  37. 37.
    Bonomi P, Pessis D, Bunting N, et al (1985): Megestrol acetate used as primary hormonal therapy in Stage D prostatic cancer. Semin Oncol 12: 36–39.PubMedGoogle Scholar
  38. 38.
    Geller J (1985): Rational for blockade of adrenal as well as testicular androgens in the treatment of advanced prostate cancer. Semin Oncol 12: 28–35.PubMedGoogle Scholar
  39. 39.
    Geller FJ,, de la Vega DJ, Albert JD et al (1984): Tissue dihydrotestosterone levels and clinical response to hormonal therapy in patients with advanced prostate cancer. J Clin Endocrinol Metab 58: 36–40.PubMedCrossRefGoogle Scholar
  40. 40.
    Brendler H (1973): Andrenalectomy and hypophysectomy for prostate cancer. Urology 2: 99–101.PubMedCrossRefGoogle Scholar
  41. 41.
    Mahoney EM, Harrison JH (1972): Bilateral adrenalectomy for paliative treatment of prostatic cancer. J Urol 108: 936–938.PubMedGoogle Scholar
  42. 42.
    Murphy GP, Reynoso G, Schoonees R, et al (1971): Hypophysectomy and adrenalectomy for disseminated prostatic carcinoma. J Urol 105: 817–819.PubMedGoogle Scholar
  43. 43.
    Robinson MRG (1980): Aminoglutethimide-medical adrenalectomy in the management of carcinoma in the prostate: a review after six years. Br J Urol 52: 328–329.PubMedCrossRefGoogle Scholar
  44. 44.
    Trachtenberg J (1984): Ketoconazole therapy in advanced prostatic cancer. J Urol 132: 61–62.PubMedGoogle Scholar
  45. 45.
    Scher H, Sternberg C (1986): Chemotherapy of urologic malignancies. Semin Urol 3: 239–280.Google Scholar
  46. 46.
    Labrie F, Dupont A, Belanger A, et al (1983): New approach in the treatment of prostate cancer: complete instead of partial withdrawl of androgens. Prostate 4: 579–594.PubMedCrossRefGoogle Scholar
  47. 47.
    Labrie F, Dupont A, Belanger A (1985): Complete androgen blockade for treatment of prostate cancer. In DeVita VT, Hellman S, Rosenberg SA (eds): Important Advances in Oncology. Philadelphia, Lippincott, p 193.Google Scholar
  48. 48.
    Perez CA, Fair WR, Ihde C, et al (1985): Cancer of the prostate. In DeVita VT, Hellman S, Rosenberg SA (eds): Principles and practice of Oncology, Second Edition. Philadephia, Lippincott, p 951.Google Scholar
  49. 49.
    Murphy GP, Buckley S, Brody MF, et al (1983): Treatment of newly diagnosed prostatic cancer patients with chemotherapy in combination with hormones versus hormones alone. Cancer 51: 1264–1272.PubMedCrossRefGoogle Scholar
  50. 50.
    Nesbit RM, Baum WC (1985): Endocrine control of prostatic carcinoma: clinical and statistical survey of 1818 cases. JAMA 143: 1317–1320.Google Scholar
  51. 51.
    Veterans Administration Cooperative Urological Research Group (1967): Treatment and survial of patients with cancer of prostate. Surg Gynecol Obstet 124: 1011–1017.Google Scholar
  52. 52.
    Labrie F, Dupont A, Lacourciere Y, et al (1986): Combined treatment with flutamide in association with medical or surgical castration. J Urol 134: 203A.Google Scholar
  53. 53.
    Isaacs JT, Coffey DS (1982): Adaptation vs. selection as the mechanism responsible for the relapse of prostatic cancer to androgen therapy as studied in the Dunning R-3327-H adenocarcinoma. Cancer Res 42: 2353–2358.PubMedGoogle Scholar
  54. 54.
    Redding TW, Schally AV (1985): Investigation of the combination of the agonist D-TRP 6-LHRH plus the antiandrogen flutamide in the treatment of Dunning R-3327-H prostate cancer model. Prostate 6: 219–230.PubMedCrossRefGoogle Scholar
  55. 55.
    Zadra J, Bruce AW, Trachtenberg J (1986): Total androgen ablation therapy in the treatment of advanced prostate cancer. J Urol 135: 201A.Google Scholar
  56. 56.
    Schroeder FH, Klijn JG, deJohn GH (1986): Metastatic cancer of the prostate managed by Buserelin Acetate versus Buserelin Acetate plus cyproterone acetate. J Urol 135: 202A.Google Scholar

Copyright information

© Kluwer Academic Publishers, Boston 1988

Authors and Affiliations

  • Pramod C. Sogani
  • Willet F. WhitmoreJr.

There are no affiliations available

Personalised recommendations