Download PDF
Deutsche Zeitschrift für Onkologie 2014; 46(02): 66-71
DOI: 10.1055/s-0033-1357653
Forschung
© Karl F. Haug Verlag in MVS Medizinverlage Stuttgart GmbH & Co. KG

Phytoöstrogenbehandlung als Therapieoption für das fortgeschrittene Prostatakarzinom

Marcus Schuermann
,
Norbert Hagg
Further Information

Publication History

Publication Date:
25 June 2014 (online)

    Permissions and Reprints

Zusammenfassung

Der Einsatz von Phytotherapeutika, insbesondere phytoöstrogenhaltige Pflanzenprodukte, spielt seit langem eine wichtige Rolle in der Behandlung von Prostataerkrankungen. Aufgrund der vielfältigen antiinflammatorischen und antiproliferativen Wirkungen wird ihr Einsatz auch in der Behandlung des Prostatakarzinoms untersucht. Während In-vitro-Daten wie auch tierexperimentelle Befunde den Einsatz in der Krebsprävention und Karzinombehandlung nahe legen, ist die klinische Wirkung beim Menschen erst ansatzweise nachgewiesen. Vieles spricht für eine Kombination mit konventionellen Prostatakarzinommedikamenten im Sinne einer Optimierung: so scheint gerade eine Kombination von Phytoöstrogenen und synthetischem Östrogen besonders wirksam in der Behandlung des hormonrefraktären Prostatakarzinoms zu sein. Die retrospektive Auswertung von 49 Fällen zeigt, dass das Präparat Sitosterol comp. in etwa 60 % eine PSA-Reduktion von mehr als 50 % innerhalb von 3 Monaten erwirkt, verbunden mit einem klinischen Ansprechen. Die mittlere erzielte Behandlungszeit liegt bei über 12 Monaten. Durch ein intensives Patientenmonitoring lassen sich die anfangs gefürchteten Nebenwirkungen synthetischer Östrogene weitgehend vermeiden. Die Behandlungsform stellt zudem eine kostengünstige Alternative dar.

Summary

Phytotherapeutic drugs have been used for long time in the treatment of prostate diseases. Due to their antiinflammatory and antiproliferative effects their influence is also being tested in the treatment of prostate cancer. While in vitro data and animal experiments support their implication in prevention and treatment of this cancer type little is known with regard to their clinical benefit in patients. There is, however, evidence for the combination of these drugs with conventional prostate cancer medication: a specific combination of phytoestrogens and synthetic estrogen proves to be promising in the treatment of hormone-refractory prostate cancer. A retrospective analysis of more than 50 patients reveals that the combination leads to a PSA reduction in approximately 60 % of the cases with more than 50 % reduction accompanied by a clinical response. The mean treatment duration is more than 12 months. Intensive patient monitoring helps to avoid most of the greatly feared side effects of synthetic estrogens. Treatment with this drug combination also proves to be an alternative which is economically attractive.

Schlüsselwörter

Prostatakarzinom - Phytotherapie - Phytoöstrogen - Polyphenole - Prävention - hormonrefraktär - Prostatakrebsbehandung

Keywords

Prostate cancer - phytotherapy - phytoestrogen - polyphenols - prevention - hormone-refractory - prostate cancer treatment
 

  • Literatur

  • 1 Adlercreutz H, Bannwart C, Wahala K et al Inhibition of human aromatase by mammalian lignans and isoflavonoid phytoestrogens. J Steroid Biochem Mol Biol 1993; 44: 147-153
    CrossrefPubMedGoogle Scholar
  • 2 Asher GN, Spelman K. Clinical utility of curcumin extract. Altern Ther Health Med 2013; 19(2): 20-22
    PubMedGoogle Scholar
  • 3 Atif B, Awad S, Fink CS. Phytosterols as anticancer dietary components: evidence and mechanism of action. J Nutr 2000; 130: 2127-2130
    PubMedGoogle Scholar
  • 4 Balunas MJ, Su B, Brueggemeier RW, Kinghorn AD. Natural products as aromatase inhibitors. Anticancer Agents Med Chem 2008; 8(6): 646-682
    CrossrefPubMedGoogle Scholar
  • 5 Berglund G. Variations in plasma phytoestrogen concentrations in European adults. J Nutr 2007; 137(5): 1293-1300
    PubMedGoogle Scholar
  • 6 Bommareddy A, Eggleston W, Prelewicz S, Antal A, Witczak Z, McCune DF, Vanwert AL. Chemoprevention of prostate cancer by major dietary phytochemicals. Anticancer Res 2013; 33(10): 4163-4174
    PubMedGoogle Scholar
  • 7 Cimino S, Sortino G, Favilla V, Castelli T, Madonia M, Sansalone S, Russo GI, Morgia G. Polyphenols: key issues involved in chemoprevention of prostate cancer. Oxid Med Cell Longev 2012; 632959. doi: 10.1155/2012/632959. Epub 2012 May 28
    PubMedGoogle Scholar
  • 8 Cook T, Sheridan WP. Development of GnRH antagonists for prostate cancer: new approaches to treatment. Oncologist 2000; 5: 162-168
    CrossrefPubMedGoogle Scholar
  • 9 de Bono JS, Logothetis CJ, Molina A, Fizazi K, North S, Chu L, Chi KN, Jones RJ, Goodman OB Jr et al COU-AA-301 Investigators. Abiraterone and increased survival in metastatic prostate cancer. N Engl J Med 2011; 364: 1995-2005
    CrossrefPubMedGoogle Scholar
  • 10 de Bono JS, Oudard S, Ozguroglu M, Hansen S, Machiels JP, Kocak I, Gravis G, Bodrogi I, Mackenzie MJ, Shen L, Roessner M, Gupta S, Sartor AO. TROPIC Investigators. Prednisone plus cabazitaxel or mitoxantrone for metastatic castration-resistant prostate cancer progressing after docetaxel treatment: a randomised open-label trial. Lancet 2010; 376: 1147-1154
    CrossrefPubMedGoogle Scholar
  • 11 Dillingham BL, McVeigh BL, Lampe JW, Duncan AM. Soy protein isolates of varying isoflavone content exert minor effects on serum reproductive hormones in healthy young men. J Nutr 2005; 135: 584-591
    PubMedGoogle Scholar
  • 12 Golshayan AR, Antonarakis ES. Enzalutamide: an evidence-based review of its use in the treatment of prostate cancer. Core Evid 2013; 8: 27-35
    PubMedGoogle Scholar
  • 13 Hoffman-Censits J, Kelly WK. Enzalutamide: a novel antiandrogen for patients with castrate-resistant prostate cancer. Clin Cancer Res 2013; 19(6): 1335-1339
    CrossrefPubMedGoogle Scholar
  • 14 Huggins C, Hodges CV. Studies on prostate cancer: I. The effect of castration, of estrogen and of androgen injection on serum phosphatases in metastatic carcinoma of the prostate. Cancer Res 1941; 1: 293-297
    PubMedGoogle Scholar
  • 15 Kolukula S, Anderson RJ. Phytoestrogens and their potential roles in prostate cancer prevention and treatment. J Cancer Sci Ther 2011; S1.  DOI: doi:10.4172/1948−5956.S1−002.
    PubMedGoogle Scholar
  • 16 Kuiper GGJM, Lemmen JG, Carlsson, BO. Corton JC, Safe SH, van der Saag PT, van der Burg B, Gustafsson JA. Interaction of estrogenic chemicals and phytoestrogens with estrogen receptor. Endocrinology 1998; 139: 4252-63
    PubMedGoogle Scholar
  • 17 Lukka H, Waldron T, Klotz L, Winquist E, Trachtenberg J. Genitourinary Cancer Disease Site Group; Cancer Care Ontario Program in Evidence-based Care. Maximal androgen blockade for the treatment of metastatic prostate cancer: a systematic review. Curr Oncol 2006; 13: 81-93
    PubMedGoogle Scholar
  • 18 Malkowicz SB. The role of diethylstilbestrol in the treatment of prostate cancer. Urology 2001; 58: 108-113
    CrossrefPubMedGoogle Scholar
  • 19 McCann SE, Ambrosone CB, Moysich KB et al Intakes of selected nutrients, foods, and phytochemicals and prostate cancer risk in Western New York. Nutr Cancer 2005; 53(1): 33-41
    CrossrefPubMedGoogle Scholar
  • 20 Miyake H, Hara I, Eto H. Clinical outcome of maximum androgen blockade using flutamide as second-line hormonal therapy for hormone-refractory prostate cancer. BJU Int 2005; 96: 791-795
    CrossrefPubMedGoogle Scholar
  • 21 Montgomery RB, Mostaghel EA, Vessella R et al Maintenance of intratumoral androgens in metastatic prostate cancer: a mechanism for castration-resistant tumor growth. Cancer Res 2008; 68: 4447-4454
    CrossrefPubMedGoogle Scholar
  • 22 Montgomery RB, Nelson PS, Lin D, Ryan CW, Garzotto M, Beer TM. Diethylstilbestrol and docetaxel: a phase II study of tubulin active agents in patients with metastatic, androgen-independent prostate cancer. Cancer 2007; 110(5): 996-1002
    CrossrefPubMedGoogle Scholar
  • 23 Morrissey C, Watson RW. Phytoestrogens and prostate cancer. Curr Drug Targets 2003; 4: 231-241
    CrossrefPubMedGoogle Scholar
  • 24 Mukhopadhyay A, Bueso-Ramos C, Chatterjee D, Pantazis P, Aggarwal BB. Curcumin downregulates cell survival mechanisms in human prostate cancer cell lines. Oncogene 2001; 20(52): 7597-7609
    CrossrefPubMedGoogle Scholar
  • 25 Nelles JL, Hu WY, Prins GS. Estrogen action and prostate cancer. Expert Rev Endocrinol Metab 2011; 6(3): 437-451
    CrossrefPubMedGoogle Scholar
  • 26 Oh WK, Kantoff PW, Weinberg V, Jones G, RiniBI. Derynck MK, Bok R et al Prospective, multicenter, randomized phase II trial of the herbal supplement, PC-SPES, and diethylstilbestrol in patients with androgen-independent prostate cancer. J Clin Oncol 2004; 22: 3705-3712
    CrossrefPubMedGoogle Scholar
  • 27 Paller CJ, Ye X, Wozniak PJ, Gillespie BK, Sieber PR, Greengold RH, Stockton BR, Hertzman BL, Efros MD, Roper RP, Liker HR, Carducci MA. A randomized phase II study of pomegranate extract for men with rising PSA following initial therapy for localized prostate cancer. Prostate Cancer Prostatic Dis 2013; 16(1): 50-55
    CrossrefPubMedGoogle Scholar
  • 28 Pantuck AJ, Leppert JT, Zomorodian N, Aronson W, Hong J, Barnard RJ, Seeram N, Liker H, Wang H, Elashoff R, Heber D, Aviram M, Ignarro L, Belldegrun A. Phase II study of pomegranate juice for men with rising prostate-specific antigen following surgery or radiation for prostate cancer. Clin Cancer Res 2006; 12(13): 4018-4026
    CrossrefPubMedGoogle Scholar
  • 29 Schuermann M. Östrogenbasierte Phytotherapie beim Prostatakarzinom. Schweiz Z Ganzheitsmed 2011; 23: 267-271
    CrossrefPubMedGoogle Scholar
  • 30 Slusarz A, Jackson GA, Day JK, Shenouda NS, Bogener JL, Browning JD, Fritsche KL, MacDonald RS, Besch-Williford CL, Lubahn DB. Aggressive prostate cancer is prevented in ERáKO mice and stimulated in ERâKO TRAMP mice. Endocrinology 2012; 153(9): 4160-4170
    CrossrefPubMedGoogle Scholar
  • 31 Taylor SE, Patel II, Singh PB et al Elevated oestrogen receptor splice variant ER α∆5 expression in tumour-adjacent hormone responsive tissue. Int J Environ Res Public Health 2010; 7(11): 3871-3889
    CrossrefPubMedGoogle Scholar
  • 32 Thelen P, Wuttke W, Seidlová-Wuttke D. Phytoestrogens selective for the estrogen receptor beta exert anti-androgenic effects in castration resistant prostate cancer. J Steroid Biochem Mol Biol 2014; 139: 290-293
    CrossrefPubMedGoogle Scholar
  • 33 van Die MD, Bone KM, Williams SG, Pirotta MV. Soy and soy isoflavones in prostate cancer: a systematic review and meta-analysis of randomised controlled trials. BJU Int 2013; Sep 5.  DOI: doi: 10.1111/bju.12435.
    PubMedGoogle Scholar
  • 34 Vitalone A, Guizzetti M, Costa LG, Tita BA. Extracts of various species of Epilobium inhibit proliferation of human prostate cells. J Pharm Pharmacol 2003; 55: 683-690
    CrossrefPubMedGoogle Scholar