Skip to main content
SpringerLink
Log in

The antiandrogen withdrawal syndrome

  • Original Paper
  • Published:
Urological Research Aims and scope Submit manuscript

Abstract

In 1989 the unanticipated agonist effect of antiandrogens on LNCaP prostate cancer cells was detected. A “flutamide withdrawal syndrome” was first described by Kelly and Scher [15], who reported a decrease in serum prostate-specific antigen (PSA) levels after the removal of flutamide from the treatment regimen. In the last few years the paradoxical response to antiandrogens has also been reported for bicalutamide, chlormadinone acetate and others. Therefore the name of the syndrome has changed to \ldantiandrogen withdrawal syndrome.\rd Several reasons such as mutations in the androgen receptor or a direct stimulatory effect of the antiandrogen for this effect have been discussed, but the exact molecular mechanism remains unclear. However, in patients with hormonally relapsed prostate cancer, a trial of \ldwithdrawal therapy\rd is required prior to the initiation of toxic therapies.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Akakura K, Akimoto S, Ohki T, Shimazaki J (1995) Antiandrogen withdrawal syndrome in prostate cancer after treatment with steroidal antiandrogen chlormadinone acetate. Urology 45:700

    Google Scholar 

  2. Belani CP, Pearl P, Whitley NO, Aisner J (1989) Tamoxifen withdrawal response. Arch Intern Med 149:449

    Google Scholar 

  3. Bissada NK, Kaczmarek AT (1995) Complete remission of hormone refractory adenocarcinoma of the prostate in response to withdrawal of diethylstilbestrol. J Urol 153:1944

    Google Scholar 

  4. Boring CC, Squires TS, Tong T (1992) Cancer statistics. CA Cancer J Clin 42:19

    Google Scholar 

  5. Bruchovsky N, Goldenberg SL, Rennie PS, Gleave M (1995) Theoretische Überlegungen und erste klinische Ergebnisse mit intermittierender Hormonbehandlung bei Patienten mit einem fortgeschrittenen Prostatakarzinom. Urologe A 34:389

    Google Scholar 

  6. Culig Z, Hobisch A, Cronauer MV, Cato AC, Hittmair A, Radmayr C, Eberle J, Bartsch G, Klocker H (1993) Mutant androgen receptor detected in an advanced-stage prostatic carcinoma is activated by adrenal androgens and progesterone. Mol Endrocrinol 7:1541

    Google Scholar 

  7. Cusan L, Gomez JL, Dupont A, Diamond P, Lemay M, Moore S, Labrie F (1994) Metastatic prostate cancer pulmonary nodules: beneficial effects of combination therapy and subsequent withdrawal of flutamide. Prostate 24:257

    Google Scholar 

  8. Dawson NA, McLeod DG (1995) Dramatic prostate specific antigen decrease in response to discontinuation of megestrol acetate in advanced prostate cancer: expansion of the antiandrogen withdrawal syndrome. J Urol 153:1946

    Google Scholar 

  9. Dupont A, Gomez JL, Cusan L, Koutsilieris M, Labrie F (1993) Response to flutamide withdrawal in advanced prostate cancer in progression under combination therapy. J Urol 150:908

    Google Scholar 

  10. Evans BAJ, Harper ME, Daniells CE, Watts CE, Matenhelia S, Green J, Griffiths K (1996) Low incidence of androgen receptor gene mutations in human prostatic tumors using single strand conformation polymorphism analysis. Prostate 28:162

    Google Scholar 

  11. Figg WD, Sartor O, Cooper MR, Thibault A, Bergan RC, Dawson N, Reed E, Myers CE (1995) Prostate specific antigen decline following the discontinuation of flutamide in patients with stage D2 prostate cancer. Am J Med 98:412

    Google Scholar 

  12. Gaddipati JP, McLeod DG, Heidenberg HB, Sesterhenn IA, Finger MJ, Moul JW, Srivastava S (1994) Frequent detection of codon 877 mutations in the androgen receptor gene in advanced prostate cancers. Cancer Res 54:2861

    Google Scholar 

  13. Herrada J, Dieringer P, Logothetis CJ (1996) Characterization of patients with androgen-independent prostatic carcinoma whose serum prostate specific antigen decreased following flutamide withdrawal. J Urol 155:620

    Google Scholar 

  14. Hobisch A, Culig Z, Radmayr C, Bartsch G, Klocker H, Hittmair A (1996) Androgen receptor status of lymph node metastases from prostate cancer. Prostate 28:129

    Google Scholar 

  15. Kelly WK, Scher HI (1993) Prostate specific antigen decline after antiandrogen withdrawal: The flutamide withdrawal syndrome. J Urol 149:607

    Google Scholar 

  16. Liebertz C, Kelly WK, Theodoulou M, Curley T, Dean L, Moyumdar M, Vlanis V, Scher HI (1995) High-dose Casodex for prostate cancer (PC): PSA declines in patients with flutamide withdrawal responses. Proc Am Soc Clin Onc 14 (abstract):603

    Google Scholar 

  17. Moul JW, Srivastava S, McLeod DG (1995) Molecular implications of the antiandrogen withdrawal syndrome. Semin Urol 13:157

    Google Scholar 

  18. Newmark JR, Hardy DO, Tonb DC, Carter BS, Epstein JI, Isaacs WB, Brown TR, Barrack ER (1992) Androgen receptor gene mutations in human prostate cancer. Proc Natl Acad Sci USA 89:6319

    Google Scholar 

  19. Nieh P (1995) Withdrawal phenomenon with the antiandrogen casodex. J Urol 153:1070

    Google Scholar 

  20. Sartor O, Cooper M, Weinberger M, Headlee D, Thibault A, Tompkins A, Steinberg S, Figg WD, Linehan WM, Myers CE (1994) Surprising activity of flutamide withdrawal, when combined with aminoglutethimide, in treatment of “hormonerefractory” prostate cancer. J Natl Cancer Inst 86:222

    Google Scholar 

  21. Sasagawa I, Satomi S (1990) Effect of high-dose medroxyprogesterone acetate on plasma hormone levels and pain relief in patients with advanced prostatic cancer. Br J Cancer 65:278

    Google Scholar 

  22. Scher HI, Kelly WK (1993) The flutamide withdrawal syndrome: Its impact on clinical trials in hormone-refractory prostatic cancer. J Clin Oncol 11:1566

    Google Scholar 

  23. Scher HI, Zhang ZF, Cohen L, Kelly KW (1995) Hormonally relapsed prostatic cancer: Lessons from the flutamide withdrawal syndrome. Adv Urol 8:61

    Google Scholar 

  24. Small EJ, Carroll PR (1994) Prostate-specific antigen decline after casodex withdrawal: evidence for an antiandrogen withdrawal syndrome. Urology 43:408

    Google Scholar 

  25. Suzuki H, Sato N, Watabe Y, Masai M, Seino S, Shimazaki J (1993) Androgen receptor gene mutations in human prostate cancer. J Steroid Biochem Mol Biol 46:759

    Google Scholar 

  26. Taplin ME, Bubley GJ, Shuster TD, Frantz ME, Spooner AE, Ogata GK, Keer HN, Balk SP (1995) Mutation of the androgen-receptor gene in metastatic androgen-independent prostate cancer. N Engl J Med 332:1393

    Google Scholar 

  27. Veldscholte J, Ris-Stalpers C, Kuiper GGJM, Jenster G, Berrevoets C, Claasen C, VanRooij HCJ, Trapman J, Brinkmann AO, Mulder E (1990) A mutation in the ligand binding domain of the androgen receptor of human LNCaP cells affects steroid binding characteristics and response to antiandrogens. Biochem Biophys Res Commun 173:534

    Google Scholar 

  28. Wilding G, Chen M, Gelmann EP (1989) Aberrant response in vitro of hormone responsive prostate cancer cells to antiandrogens. Prostate 14:103

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Dept. of Urology, Technical University of Dresden Fetscherstr 74, D-01307, Dresden, Germany

    M. P. Wirth & S. E. Froschermaier

Authors
  1. M. P. Wirth
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. S. E. Froschermaier
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wirth, M.P., Froschermaier, S.E. The antiandrogen withdrawal syndrome. Urol. Res. 25 (Suppl 2), S67–S71 (1997). https://doi.org/10.1007/BF00941991

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00941991

Key words

Search

Navigation