TumorDiagnostik & Therapie 2012; 33(7): 417-422
DOI: 10.1055/s-0032-1325417
Thieme Onkologie aktuell
© Georg Thieme Verlag KG Stuttgart · New York

Die intermittierende Androgenblockade beim fortgeschrittenen Prostatakarzinom – eine Übersicht

Intermittent Androgen Deprivation in Advanced Prostate Cancer – A Review
J. M. Wolff
Urologische Klinik, AKH Viersen, Viersen
› Author Affiliations
Further Information

Publication History

Publication Date:
15 October 2012 (online)

Zusammenfassung

Derzeit ist die Androgenblockade der Goldstandard bei der Behandlung des fortgeschrittenen, metastasierten Prostatakarzinoms. Es handelt sich dabei um eine palliative Therapie, bei der innerhalb von 2 Jahren mehr als die Hälfte der Patienten eine Progression erleidet, da der Tumor zunehmend hormonunempfindlich wird. Die Arbeitsgruppe um Bruchovsky postulierte Anfang der 90er-Jahre, dass man durch den intermittierenden Einsatz der Androgenblockade das apoptotische Potenzial erhalten könne und man somit die Entwicklung der Hormonunempfindlichkeit und die Tumorprogression hinauszögern könne. Ebenso sollte sich die Lebensqualität der Patienten durch den periodischen Wechsel von Phasen mit und ohne Behandlung verbessern lassen. Aufgrund der derzeitigen Daten der seither durchgeführten Phase-II- und -III-Studien ist die IAB (intermittierende Androgenblockade) genauso effektiv wie die KAB (kontinuierliche Androgenblockade). Obgleich die Datenbasis für die Lebensqualität und das Gesamtüberleben noch limitiert ist, scheinen die Ergebnisse zumindest vergleichbar zu sein. Unklar ist, welche Patienten am meisten von einer IAB profitieren. Hier sind die Endergebnisse der laufenden Phase-III-Studie abzuwarten.

Abstract

At present androgen ablation therapy is the therapy of choice for the treatment of metastatic prostate cancer. However, in more than 50 % of the patients the disease will ultimately progress within 2 years.On the basis of the postulation from Bruchovsky et al. that intermittent androgen deprivation maintains the apoptotic potential, this may lead to a delay in tumour progression. By periodically changing phases from on to off the treatment quality of life for the patient may be improved. Most recent clinical data of phase II and III studies imply that IAB is equal effective as CAB. Although data about quality of life and overall survival are still limited, results seem to be comparable. In order to decide which patient groups are most likely to benefit from IAB, final phase III results need to be available.

 
  • Literatur

  • 1 Huggins C, Hodges CV. Studies on prostatic cancer I: The effect of castration, estrogen and androgen injection on serum phosphatases in metastatic carcinoma of the prostate. Cancer Res 1941; 1: 293-297
  • 2 Scott WW, Menon M, Walsh PC. Hormonal therapy of prostatic cancer. Cancer 1990; 45: 1929-1933
  • 3 Denis L, Murphy GP. Overview over phase III trials on combined androgen treatment in patients with metastatic prostate cancer. Cancer Suppl 1993; 72: 3888-3895
  • 4 Bruchovsky N, Rennie PS, Coldman AJ et al. Effects of androgen withdrawal on the stem cell composition of the Shionogi carcinoma. Cancer Res 1990; 50: 2275-2282
  • 5 Akakura K, Bruchovsky N, Goldenberg SL et al. Effects of intermittent androgen suppression androgen-dependent tumors: apoptosis and serum prostate specific antigen. Cancer 1993; 71: 2782-2790
  • 6 Bruchovsky N, Snoek R, Rennie PS et al. Control of tumor progression by maintenance of apoptosis. The Prostate 1996; 6: 13-21
  • 7 Noble RL. Hormonal control of growth and progression in tumors of Nb rats and a theory of action. Cancer Research 1977; 37: 82-94
  • 8 Rennie PS, Bruchovsky N, Buttgan R. Gene expression during the early phases of regression of the androgen-dependent Shionogi mouse mammary carcinoma. Cancer Research 1988; 48: 6309-6313
  • 9 Young D, Montgomery BT, Andrews PE. Hormonal regulation of prostate specific antigen messenger RNA in human prostatic adenocarcinoma cell line LNCaP. Cancer Research 1991; 51: 3748-3752
  • 10 Sato N, Gleave ME, Goldenberg SL et al. Intermittent androgen suppression delays time to androgen-independent progression in the LNCaP prostate tumour model. J Urol 1995; 153: 282A-282A
  • 11 Russo P, Liguori G, Heston WDW et al. Effects of intermittent disethylstilbestrol diphosphate administration on the R3327 rat prostatic carcinoma. Cancer Res 1987; 47: 5967-5970
  • 12 Trachtenberg J. Experimental treatment of prostatic cancer by intermittent hormonal therapy. J Urol 1987; 137: 785-788
  • 13 Stoll BA. Palliation by castration or by hormone administration. In: Stoll BA. Breast Cancer Management Early and Late. Chicago: Chicago Year Book Medical; 1977: 133-146
  • 14 Bruchovsky N, Klotz L, Crook J et al. Locally advanced prostate cancer-biochemical results from a prospective phase II study of intermittent androgen supression for men with evidence of prostate-specific antigen recurrence after radiotherapy. Cancer 2007; 109: 858-867
  • 15 Vahlensieck W, Wagner W, Lehmann HD. Comparison between continuous and intermittentadministration of Estracyt in the treatment of carcinoma of the prostate. Urol Res 1985; 13: 209-212
  • 16 Klotz LH, Herr HW, Morse Jr MU et al. Intermittent endocrine therapy for advanced prostate cancer. Cancer 1986; 58: 2546-2550
  • 17 Goldenberg SL, Gleave ME, Taylor D et al. Clinical experience with intermittent androgen suppression in prostate cancer: minumum of 3 years follow-up. Mol Urol 1999; 3: 287-292
  • 18 Cury FL, Souhami L, Rajan R. Intermittent androgen ablation in patients with biochemical failure after pelvic radiotherapy for localized prostate cancer. Int J Radiat Oncol Biol Phys 2006; 64: 842-848
  • 19 Crook JM, Szumacher E, Malone S et al. Intermittent androgen suppression in the management of prostate cancer. Urology 1999; 53: 530-534
  • 20 Bales GT, Sinner MD, Kim JH et al. Impact of intermittent androgen deprivation on quality of life. J Urol 1996; 155: A1069-A1069
  • 21 Zerbib M, Conquy S, Gerhaud PF. Efficacy and effect on quality of life of intermittent androgen deprivation for prostate cancer treatment. Eur Urol 1999; 35 (Suppl. 01) A54-A54
  • 22 Da Silva FM, Bono A, Whelan P et al. Phase III study of intermittent MAB vs. contiuous MAB. J Urol 2011; 185: 23-23
  • 23 Abrahamsson PA. Potential Benefits of intermittent androgen suppression therapy in the treatment of prostate cancer: a systematic review of the literature. Eur Urol 2010; 57: 49-59
  • 24 Shaw GL, Wilson P, Cuzick J. International study into the use of intermittent hormone therapy of carcinoma of the prostate: a meta-analysis of 1446 patients. BJU Int 2007; 99: 1056-1065
  • 25 De Leval J, Boca P, Yousef E. Intermittent versus continuous total androgen blockade in the treatment of patients with advanced hormone-naive prostate cancer; results of a prospective randomised multicenter trial. Clin Prostate Cancer 2002; 1: 163-171
  • 26 Langenhuijsen JF, Schasfoort EMC, Heathcote P. Intermittent androgen suppression in patients with advanced prostate cancer: an update of the TULP survival data. abstract, 23rd Congress of the EAU Milan, Italy: 2008
  • 27 Mottet N, Goussard M, Loulidi S, Wolff J. Intermittent versus continuous maximal blockade in metastatic (D2) prostate cancer patients, a randomized trial. Paper presented at 24th Congress of the EAU Stockholm, Sweden: 2009
  • 28 Da Silva F, Bono AV, Whelan P. Intermittent androgen depriviation for locally advanced and metastatic prostate cancer: results from a randomised phase 3 study of the South European Uroncological Group. Eur Urol 2009; 55: 1269-1277
  • 29 Gulley LJ, Figg WD, Steinberg SM. A prospective analysis of the time to normalization of serum androgens following 6 months of androgen deprivation therapy in patients on a randomized phase III clinical trial using limited hormonal therapy. J Urol 2005; 173: 1567-1571
  • 30 Miller K, Steiner U, Lingnau A. Randomised prospective study of intermittent versus continuous androgen suppression in advanced prostate cancer (abstract 5105). Presented at: American Society of Clinical Oncology; June 1–5 Chicago, IL, USA: 2007
  • 31 Da Silva C, Bono A, Whelan P et al. Phase III study of intermittent MAB versus continuous MAB international cooperative study. Eur Urol 1999; 35 (Suppl. 02) A54-A54
  • 32 Verhagen PCMS, Wissenburg LD, Wildhagen MF. Quality of life effects of intermittent and continuous hormonal therapy by cyproterone acetate (CPA) for metastatic prostate cancer (abstract 541). Presented at: 23rd Annual Congress of the European Association of Urology; March 26–29 Milan, Italy: 2008
  • 33 Conti PD, Atallah AN, Arruda H, Soares BG, El DibRP, Wilt TJ. Intermittent versus continuous androgen suppression for prostatic cancer. Cochrane Database Syst Rev; 2007 CD005009
  • 34 Gleave M, Klotz L, Taneja SS. The continued debate: intermittent vs. continuous hormonal ablation for metastatic prostate cancer. Urol Oncol 2009; 27: 81-86