Onkologie. 2014:8(2):75-79

Hormonal therapy for castration-resistant prostate cancer, are there lines of therapy?

Michaela Matoušková, Miroslav Hanuš
Urocentrum Praha

The knowledge of hormone dependence of prostate cancer and the possibilities of interfering with it were described as early as the

1940s. In a large proportion of patients, surgical castration is replaced by medical castration by means of LHRH agonists. In order to

reduce testosterone level fluctuations during LHRH administration (mini flare-up phenomenon) and, thus, the action of non-castrate

testosterone levels during treatment on the androgen receptor, administration of LHRH antagonists is more convenient. Despite a good

and often long-term response to hormonal therapy, failure of the treatment modality occurs. The monotherapy administered initially can

be extended to maximum androgen blockade and, thus, to prolongation of the effect of hormonal therapy. Nevertheless, a malignant

tumour acquires different growth characteristics, fundamentally altering the disease prognosis and becoming castration-resistant (CRPC),

i.e. progressive with castrate testosterone levels. In the early millennium, first-line therapy for castration-resistant prostate cancer was

standardized. Administration of docetaxel with prednisone was the first treatment to have resulted in prolonged survival in patients with

CRPC. Newly registered medicinal products are compared with this regimen in terms of efficacy and the rates of adverse effects. Regimens

with immunotherapy, a novel cytotoxic drug cabazitaxel, and, in particular, the new hormonal products abiraterone and enzalutamide

are gradually emerging. A large number of agents alone or in combination with standard therapy are being investigated in clinical trials.

In the case of drugs that have already been approved, ongoing trials should address issues concerning the optimal duration of use

and the sequence of treatment. Administration of bone-metabolism modulating agents is an integral part of the treatment for mCRPC.

Keywords: castration-resistant prostate cancer (CRPC), hormonal therapy, chemotherapy, targeted therapy, novel agents

Published: May 10, 2014  Show citation

ACS AIP APA ASA Harvard Chicago Chicago Notes IEEE ISO690 MLA NLM Turabian Vancouver
Matoušková M, Hanuš M. Hormonal therapy for castration-resistant prostate cancer, are there lines of therapy? Onkologie. 2014;8(2):75-79.
Download citation

References

  1. Huggins C, Hodges C. Studies on prostatic 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.
  2. Tannock IF, de Witt R, Berry WR, et al. Docetaxel plus prednisone or Mitoxantrone plus prednisone for advanced prostate cancer. New Engl J Med 2004; 351: 1502-1512. Go to original source... Go to PubMed...
  3. Massard Ch, Fizazi K. Targeting Continued Androgen Receptor Signaling in Prostate Cancer. Clin Cancer Res 2011; 17: 3876. Go to original source... Go to PubMed...
  4. Lavery DN, Bevan CL. Androgen receptor signalling in prostate cancer: the functional consequences of acetylation. J Biomed Biotechnol 2011; 2011: 862125. Epub 2010 Dec 28. Go to original source... Go to PubMed...
  5. Attard G, Sarker D, Reid A, et al. Improving the outcome of patients with castration-resistant prostate cancer through rational drug development. Br J Cancer 2006; 95: 767-774. Go to original source... Go to PubMed...
  6. Parsons SJ, Parsons JT. Src family kinases, key regulators of signal transduction. Oncogene 2004; 23: 7906-7909. Go to original source... Go to PubMed...
  7. Dutt SS, Gao AC. Molecular mechanisms of castration-resistant prostate cancer progression. Future Oncol 2009; 5: 1403-1413. Go to original source... Go to PubMed...
  8. Fizazi K, Scher HI, Molina A, et al. Final overall survival (OS) analysis of COU-AA-301, a phase 3 study of abiraterone acetate plus prednisone in patients with metastatic castration-resistant prostate cancer (mCRPC) pretreated with docetaxel. Lancet Oncol 2012; 13(10): 983-992. Go to original source... Go to PubMed...
  9. Scher HI, Fizzzazi K, Saad F, et al. Increased survival with enzalutamide in prostate cancer after chemotherapy. N Engl J Med. 2012; 367(13): 1187-1197. Go to original source... Go to PubMed...
  10. Ang JE, Olmos D, de Bono JS. CYP17 blockade by abiraterone: further evidence for frequent continued hormone-dependence in castration-resistant prostate cancer. Br J Cancer. 2009; 100(5): 671-675. Go to original source... Go to PubMed...
  11. Beer, et al. Enzalutamide in men with chemotherapy-naive metastatic prostate cancer (mCRPC): Results of phase III PREVAIL study. J Clin Oncol 32, 2014(suppl 4; abstr LBA1). Go to original source...
  12. Ryan CJ, Smith MR, De Bono JS, et al. Interim Analysis Results of COU-AA-302, a Randomized, Phase 3 Study of Abiraterone Acetate (AA) in Chemotherapy-Na?ve Patients With Metastatic Castration-Resistant Prostate Cancer (mCRPC) N Engl J Med 2013; 368(2): 138-148.
  13. Dreicer R, MacLean D, Suri A et al. Phase 1/2 Trial of Orteronel (TAK-700) - an Investigational 17,20-Lyase Inhibitor - in Patients with Metastatic Castration-Resistant Prostate Cancer. Clin Cancer Res Published OnlineFirst January 13, 2014. Go to original source... Go to PubMed...
  14. Lissbrant IF, Garmo H, et al. Population-based study on use of chemotherapy in men with castration resistant prostate cancer Acta Oncol. 2013; 52(8): 1593-1601. Go to original source... Go to PubMed...
  15. Noonan KL, North S, Bitting RL, et al. Clinical activity of abiraterone acetate in patients with metastatic castration-resistant prostate cancer progressing after enzalutamide Ann Oncol. 2013; 24(7): 1802-1807. Go to original source... Go to PubMed...
  16. Schrader AJ, Boegemann M, Ohlmann CH, et al. Enzalutamide in castration-resistant prostate cancer patients progressing after docetaxel and abiraterone. Eur Urol. 2014 Jan; 65 (1): 30-6. doi: 10.1016/j.eururo.2013.06.042. Epub 2013 Jul 2. Go to original source... Go to PubMed...
  17. Mezynski J, Pezaro C, Bianchini D, et al. Antitumour activity of docetaxel following treatment with the CYP17A1 inhibitor abiraterone: clinical evidence for cross-resistance? Ann Oncol. 2012; 23(11): 2943-2947. Go to original source... Go to PubMed...
  18. Pezaro CJ, Omlin AG, Altavilla A, et al. Activity of Cabazitaxel in Castration-resistant Prostate Cancer Progressing After Docetaxel and Next-generation Endocrine Agents Eur Urol. 2013 Dec 17. pii: S0302-2838(13)01308-0. doi: 10.1016/j.eururo.2013.11.044. [Epub ahead of print]. Go to original source... Go to PubMed...
  19. Angelergues A, et al. Prognostic factors of survival in patients with metastatic castration resistant prostate cancer (mCRPC) treated with cabazitaxel: Sequencing might matter. J Clin Oncol. 2013; 31(Suppl 6): Abstract 5063. Go to original source...
  20. Loriot Y, Bianchini D, Ileana E, et al. Antitumour activity of abiraterone acetate against metastatic castration-resistant prostate cancer progressing after docetaxel and enzalutamide (MDV3100). Ann Oncol. 2013; 24(7): 1807-1812. Go to original source... Go to PubMed...
  21. Rathkopf DE, Smith MR, De Bono JS, et al: Updated interim analysis (IA) of COU-AA-302, a randomized phase III study of abiraterone acetate (AA) in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) without prior chemotherapy. J Clin Oncol 31, 2013(suppl 6; abstr 5). Go to original source...
  22. De Bono JS, Oudard S, Ozguroglu M, et al. 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. Go to original source... Go to PubMed...
  23. Kantoff PW, Gitano CS, Shore ND, el al. Sipuleucel-T Immunotherapy for Castration-Resistant Prostate Cancor. N Engl J Med 2010; 363: 411-422. Go to original source... Go to PubMed...
  24. Parker C, Nilsson S, Heinrich D, et al. Alpha Emitter Radium-223 and Survival in Metastatic Prostate Cancer. N Engl J Med 2013;369:213-23. DOI: 10.1056/NEJMoa1213755. Go to original source... Go to PubMed...




Oncology

Madam, Sir,
please be aware that the website on which you intend to enter, not the general public because it contains technical information about medicines, including advertisements relating to medicinal products. This information and communication professionals are solely under §2 of the Act n.40/1995 Coll. Is active persons authorized to prescribe or supply (hereinafter expert).
Take note that if you are not an expert, you run the risk of danger to their health or the health of other persons, if you the obtained information improperly understood or interpreted, and especially advertising which may be part of this site, or whether you used it for self-diagnosis or medical treatment, whether in relation to each other in person or in relation to others.

I declare:

  1. that I have met the above instruction
  2. I'm an expert within the meaning of the Act n.40/1995 Coll. the regulation of advertising, as amended, and I am aware of the risks that would be a person other than the expert input to these sites exhibited


No

Yes

If your statement is not true, please be aware
that brings the risk of danger to their health or the health of others.