Zusammenfassung
Nach durchschnittlich 18–24 Monaten kommt es beim Prostatakarzinom unter Androgensuppression zum PSA-Progress. Bei ungefähr der Hälfte der Patienten kann in diesem hormonunabhängigen Stadium durch eine sekundäre Hormonmanipulation eine erneute PSA-Regression über 6–12 Monate erreicht werden, bevor das Stadium der totalen Hormonrefraktärität eintritt.
Nach Progress unter kompletter Androgenablation kann durch das Absetzen des Antiandrogens in 40% der Fälle ein temporärer Regress erzielt werden. Die Gabe eines alternativen Antiandrogens führt bei 80% der Responder auf einen Antiandrogenentzug erneut zu einem PSA-Rückgang. Die Hemmung der adrenalen Testosteronfunktion mit Ketoconazol kann ebenfalls den Krankheitsprogress hinauszögern. Auch die transdermale Applikation von Östrogenen führt über Modulation der LHRH- und Testosteronausschüttung sowie über eine direkte Wirkung auf die Tumorzellen zu einer vorübergehenden Kontrolle der Tumoraktivität. Neuere Therapieformen wie z. B. Somatostatinanaloga beeinflussen das Mikro-Environment der Tumorzellen und bewirken so eine verstärkte Wirkung der Antitumortherapie.
Abstract
After an average of 18–24 months under androgen suppression therapy, almost all patients with prostate cancer show a PSA progress. At this hormone-independent stage, a PSA regress can be achieved by secondary hormonal manipulation in approximately 50% of patients for 6–12 months before they become hormone-refractory.
After progress under complete androgen ablation, in 40% of cases a temporary regress can be achieved by discontinuing of the anti-androgen. The administration of an alternative anti-androgen results in a PSA decrease in 80% of the patients responding to anti-androgen deprivation. Inhibition of the adrenal testosterone synthesis by oral administration of ketoconazol can further delay disease progression. Transdermal application of estrogens also allows temporary control of tumor activity by modulating the LHRH and testosterone release as well as directly effecting tumor cell apoptosis. Recent therapeutic modalities as for example somatostatin analogues influence the microenvironment of tumor cells and thereby intensify the effect of anti-tumor therapy.
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Literatur
Epstein JI, Partin AW, Sauvageot J, Walsh PC (1996) Prediction of progression following radical prostatectomy. A multivariate analysis of 721 men with long-term follow-up. Am J Surg Pathol 20(3):286–292
Hedlund PO, Ala-Opas M, Brekkan E et al (2002) Parenteral estrogen versus combined androgen deprivation in the treatment of metastatic prostatic cancer – Scandinavian Prostatic Cancer Group (SPCG) Study No. 5. Scand J Urol Nephrol 36(6):405–413
Heidenreich A, Aus G, Bolla M et al (2008) EAU guidelines on prostate cancer. Eur Urol 53(1):68–80
Heidenreich A, Ohlmann CH (2005) Treatment options for hormone-refractory prostate cancer. Urologe A 44(11):1303–1304, 1306–1314
Hussain M, Wolf M, Marshall E et al (1994) Effects of continued androgen-deprivation therapy and other prognostic factors on response and survival in phase II chemotherapy trials for hormone-refractory prostate cancer: a Southwest Oncology Group report. J Clin Oncol 12(9):1868–1875
Kelly WK, Scher HI (1993) Prostate specific antigen decline after antiandrogen withdrawal: the flutamide withdrawal syndrome. J Urol 149(3):607–609
Mitsiades CS, Koutsilieris M (2001) Molecular biology and cellular physiology of refractoriness to androgen ablation therapy in advanced prostate cancer. Expert Opin Investig Drugs 10(6):1099–1115
Oh WK (2002) The evolving role of estrogen therapy in prostate cancer. Clin Prostate Cancer 1(2):81–89
Petrylak DP, Tangen CM, Hussain MH et al (2004) Docetaxel and estramustine compared with mitoxantrone and prednisone for advanced refractory prostate cancer. N Engl J Med 351(15):1513–1520
Reddy GP, Barrack ER, Dou QP et al (2006) Regulatory processes affecting androgen receptor expression, stability and function: potential targets to treat hormone-refractory prostate cancer. J Cell Biochem 98(6):1408–1423
Ricke WA, Wang Y, Cunha GR (2007) Steroid hormones and carcinogenesis of the prostate: the role of estrogens. Differentiation 75(9):871–882
Schilling D, Kufer R, Kruck S et al (2008) Somatostatin analogs for the treatment of advanced, hormone-refractory prostate cancer: a possibility for secondary hormonal ablation?. Urologe A 47(10):1334–1338
Small EJ, Halabi S, Dawson NA et al (2004) Antiandrogen withdrawal alone or in combination with ketoconazole in androgen-independent prostate cancer patients: a phase III trial (CALGB 9583). J Clin Oncol 22(6):1025–1033
Small EJ, Vogelzang NJ (1997) Second-line hormonal therapy for advanced prostate cancer: a shifting paradigm. J Clin Oncol 15(1):382–388
Smith DC, Dunn RL, Strawderman MS, Pienta KJ (1998) Change in serum prostate-specific antigen as a marker of response to cytotoxic therapy for hormone-refractory prostate cancer. J Clin Oncol 16(5):1835–1843
Tannock IF, de Wit R, Berry WR et al (2004) Rosenthal, and M.A. Eisenberger, Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. N Engl J Med 351(15):1502–1512
Taylor CD, Elson P, Trump DL (1993) Importance of continued testicular suppression in hormone-refractory prostate cancer. J Clin Oncol 11(11):2167–2172
Wilkinson S, Chodak G (2004) An evaluation of intermediate-dose ketoconazole in hormone refractory prostate cancer. Eur Urol 45(5):581–584
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Schilling, D., Gakis, G., Bökeler, U. et al. Sekundäre Hormonablation beim hormonunabhängigen Prostatakarzinom. Urologe 48, 183–190 (2009). https://doi.org/10.1007/s00120-009-1940-5
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DOI: https://doi.org/10.1007/s00120-009-1940-5