Clinical and Translational Oncology

, Volume 18, Issue 10, pp 972–980 | Cite as

Role of taxanes in advanced prostate cancer

  • J. Cassinello
  • J. Carballido Rodríguez
  • L. Antón Aparicio
Review Article


Advanced prostate cancer is an androgen-dependent disease for which the initial treatment is an androgen deprivation maneuver. However, some primary resistances to hormonal treatment occur with increasing incidence throughout the evolution of the disease. The taxanes, docetaxel and cabazitaxel, exert their action at multiple levels at the tumor cell: besides inhibiting the mitosis and inducing the cell death, they induce the nuclear accumulation of FOXO1, a potent nuclear factor that acts against the activation of androgen receptor inhibiting the transcription of AR-V7 variant associated with the development of resistances to abiraterone and enzalutamide. Docetaxel, as first-line therapy, and cabazitaxel, as second-line therapy, have demonstrated to increase the survival in castration-resistant prostate cancer. The results from last studies either on high-risk localized disease or on androgen-sensitive tumors demonstrate the increasing role of taxanes at earlier states of prostate cancer.


Prostate cancer Docetaxel Cabazitaxel Androgen deprivation therapy AR splice variant 



Medical writing assistance was provided by PIVOTAL S.L, funded by Sanofi. The authors are fully responsible for all content and editorial decisions for this manuscript. The authors indicate that they do not have any conflict of interests to declare.

Compliance with ethical standards

Informed consent

This article is a review of published studies, thus achievement of the patient Informed consent was not necessary.

Research involving human participants and/or animals

This article does not contain any studies with human participants or animals performed by any of the authors.


  1. 1.
    Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, et al. GLOBOCAN 2012 v1.0, cancer incidence and mortality worldwide: IARC CancerBase No. 11. 2013.
  2. 2.
    Prostate Cancer Trialists’ Collaborative Group. Maximum androgen blockade in advanced prostate cancer: an overview of the randomised trials. Lancet. 2000;355(9214):1491–8.CrossRefGoogle Scholar
  3. 3.
    Seidenfeld J, Samson DJ, Hasselblad V, Aronson N, Albertsen PC, Bennett CL, et al. Single-therapy androgen suppression in men with advanced prostate cancer: a systematic review and meta-analysis. Ann Intern Med. 2000;132(7):566–77.CrossRefPubMedGoogle Scholar
  4. 4.
    Chi KN, Chin JL, Winquist E, Klotz L, Saad F, Gleave ME. Multicenter phase II study of combined neoadjuvant docetaxel and hormone therapy before radical prostatectomy for patients with high risk localized prostate cancer. J Urol. 2008;180(2):565–70.CrossRefPubMedGoogle Scholar
  5. 5.
    Sweeney C, Chen Y, Carducci MA, Liu G, Jarrard FD, Eisenberger MA, et al. Impact on overall survival with chemohormonal therapy versus hormonal therapy for hormone-sensitive newly metastatic prostate cancer: an ECOG-led phase III randomized trial. 50th annual meeting of American Society of Clinical Oncology (June 2014). Abstract LBA2. 2015.Google Scholar
  6. 6.
    Tannock IF, de WR, Berry WR, Horti J, Pluzanska A, Chi KN, et al. Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. N Engl J Med. 2004;351(15):1502–12.CrossRefPubMedGoogle Scholar
  7. 7.
    de Bono JS, Oudard S, Ozguroglu M, Hansen S, Machiels JP, Kocak I, 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(9747):1147–54.CrossRefPubMedGoogle Scholar
  8. 8.
    Fitzpatrick JM, de Wit R. Taxane mechanisms of action: potential implications for treatment sequencing in metastatic castration-resistant prostate cancer. Eur Urol. 2014;65(6):1198–204.CrossRefPubMedGoogle Scholar
  9. 9.
    Antonarakis ES, Lu C, Luber B, Wang H, Chen Y, Nakazawa M, et al. Androgen receptor splice variant 7 and efficacy of taxane chemotherapy in patients with metastatic castration-resistant prostate cancer. JAMA Oncol. 2015;1(5):582–91.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Beltran H, Rickman DS, Park K, Chae SS, Sboner A, MacDonald TY, et al. Molecular characterization of neuroendocrine prostate cancer and identification of new drug targets. Cancer Discov. 2011;1(6):487–95.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Tagawa ST. Neuroendocrine prostate cancer after hormonal therapy: knowing is half the battle. J Clin Oncol. 2014;32(30):3360–4.CrossRefPubMedGoogle Scholar
  12. 12.
    Pezaro CJ, Omlin A, Lorente D, Nava RD, Ferraldeschi R, Bianchini D, et al. Visceral disease in castration-resistant prostate cancer. Eur Urol. 2014;65(2):270–3.CrossRefPubMedGoogle Scholar
  13. 13.
    Zong Y, Goldstein AS. Adaptation or selection—mechanisms of castration-resistant prostate cancer. Nat Rev Urol. 2013;10(2):90–8.CrossRefPubMedGoogle Scholar
  14. 14.
    Arora VK, Schenkein E, Murali R, Subudhi SK, Wongvipat J, Balbas MD, et al. Glucocorticoid receptor confers resistance to antiandrogens by bypassing androgen receptor blockade. Cell. 2013;155(6):1309–22.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Sandler HM, Hu C, Rosenthal SA, Sartor O, Gomella LG, Amin M, et al. A phase III protocol of androgen suppression (AS) and 3DCRT/IMRT versus AS and 3DCRT/IMRT followed by chemotherapy (CT) with docetaxel and prednisone for localized, high-risk prostate cancer (RTOG 0521). J Clin Oncol. 2015;33 (suppl; abstr LBA5002).Google Scholar
  16. 16.
    James ND, Sydes MR, Mason MD, Clarke NW, Dearnaley DP, Spears MR, et al. Docetaxel and/or zoledronic acid for hormone-naïve prostate cancer: first overall survival results from STAMPEDE (NCT00268476). J Clin Oncol. 2015;33 (suppl; abstr 5001).Google Scholar
  17. 17.
    NCCN. Prostate cancer update. NCCN guidelines version 1. 2015.Google Scholar
  18. 18.
    Gravis G, Fizazi K, Joly F, Oudard S, Priou F, Esterni B, et al. Androgen-deprivation therapy alone or with docetaxel in non-castrate metastatic prostate cancer (GETUG-AFU 15): a randomised, open-label, phase 3 trial. Lancet Oncol. 2013;14(2):149–58.CrossRefPubMedGoogle Scholar
  19. 19.
    Heidenreich A, Bastian PJ, Bellmunt J, Bolla M, Joniau S, Mason MD, et al. European association of urology: guidelines of prostate cancer 2012. 2012.
  20. 20.
    Ryan CJ, Smith MR, de Bono JS, Molina A, Logothetis CJ, de SP, et al. Abiraterone in metastatic prostate cancer without previous chemotherapy. N Engl J Med. 2013;368(2):138–48.CrossRefPubMedGoogle Scholar
  21. 21.
    Beer TM, Armstrong AJ, Rathkopf DE, Loriot Y, Sternberg CN, Higano CS, et al. Enzalutamide in metastatic prostate cancer before chemotherapy. N Engl J Med. 2014;371(5):424–33.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Tannock IF, Osoba D, Stockler MR, Ernst DS, Neville AJ, Moore MJ, et al. Chemotherapy with mitoxantrone plus prednisone or prednisone alone for symptomatic hormone-resistant prostate cancer: a Canadian randomized trial with palliative end points. J Clin Oncol. 1996;14(6):1756–64.PubMedGoogle Scholar
  23. 23.
    Berthold, Pond GR, Soban F, de WR, Eisenberger M, Tannock IF. Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer: updated survival in the TAX 327 study. J Clin Oncol. 2008;26(2):242–5.CrossRefPubMedGoogle Scholar
  24. 24.
    Kellokumpu-Lehtinen PL, Harmenberg U, Joensuu T, McDermott R, Hervonen P, Ginman C, et al. 2-Weekly versus 3-weekly docetaxel to treat castration-resistant advanced prostate cancer: a randomised, phase 3 trial. Lancet Oncol. 2013;14(2):117–24.CrossRefPubMedGoogle Scholar
  25. 25.
    Oudard S, Kramer G, Creppy L, Loriot Y, Steinbjoern H, Holmberg M, et al. Management of metastatic castration-resistant prostate cáncer (mCRPC) after an initial good response to first-line docetaxel: a retrospective study on 270 patients. Eur J Cancer. 2011;47(Suppl 1):abstract 7049.Google Scholar
  26. 26.
    Bahl A, Oudard S, Tombal B, Ozguroglu M, Hansen S, Kocak I, et al. Impact of cabazitaxel on 2-year survival and palliation of tumour-related pain in men with metastatic castration-resistant prostate cancer treated in the TROPIC trial. Ann Oncol. 2013;24(9):2402–8.CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Chi KN, de Bono JS, Bahl A, Oudard S, Tombal B, Ozguroglu M, et al. Analysis of overall survival for patients with different prognostic risk factors treated with cabazitaxel and prednisone after docetaxel in the TROPIC trial. Ann Oncol. 2014;25(Suppl 4):iv255–79 (Poster 771P).Google Scholar
  28. 28.
    Heidenreich A, Bracarda S, Mason M, Ozen H, Sengelov L, Van OI, et al. Safety of cabazitaxel in senior adults with metastatic castration-resistant prostate cancer: results of the European compassionate-use programme. Eur J Cancer. 2014;50(6):1090–9.CrossRefPubMedGoogle Scholar
  29. 29.
    Perez Valderrama B, Mellado B, Juan MJ, Fernandez O, Fernandez-Parra E, Ochoa de Olza M, et al. Preliminary results of a phase II study of weekly cabazitaxel in “unfit” metastatic castration resistant prostate cancer (mCRPC) patients after docetaxel treatment (SOGUG-CABASEM trial). Ann Oncol. 2014;25(suppl 4):iv270 (783P).Google Scholar
  30. 30.
    Castellano D, Anton Aparicio LM, Esteban E, Sanchez-Hernandez A, Germa JR, Batista N, et al. Cabazitaxel for metastatic castration-resistant prostate cancer: safety data from the Spanish expanded access program. Expert Opin Drug Saf. 2014;13(9):1165–73.CrossRefPubMedGoogle Scholar
  31. 31.
    Oudard S, Angelergues A, Gonzalez Maeso I, Delanoy N, Flechon A, Ozguroglu M, et al. Prognostic factors for survival and sequencing of life extending therapies in mCRPC patients in post-docetaxel setting. Ann Oncol. 2014;25(suppl 4):iv255–79 (789 P).Google Scholar
  32. 32.
    Sonpavde G, Bhor M, Hennessy D, Bhowmik D, Shen L, Nicacio L, et al. Sequencing of cabazitaxel and abiraterone acetate after docetaxel in metastatic castration-resistant prostate cancer: treatment patterns and clinical outcomes in multicenter community-based US oncology practices. Clin Genitourin Cancer. 2015;13(4):309–18.CrossRefPubMedGoogle Scholar
  33. 33.
    Wissing MD, Coenen JL, van den BP, Westgeest HM, van den Eertwegh AJ, Van OI, et al. CAST: a retrospective analysis of cabazitaxel and abiraterone acetate sequential treatment in patients with metastatic castrate-resistant prostate cancer previously treated with docetaxel. Int J Cancer. 2015;136(6):E760–72.CrossRefPubMedGoogle Scholar
  34. 34.
    Maines F, Caffo O, Veccia A, Trentin C, Tortora G, Galligioni E, et al. Sequencing new agents after docetaxel in patients with metastatic castration-resistant prostate cancer. Crit Rev Oncol Hematol. 2015;96(3):498–506.CrossRefPubMedGoogle Scholar
  35. 35.
    Mezynski J, Pezaro C, Bianchini D, Zivi A, Sandhu S, Thompson E, et al. Antitumour activity of docetaxel following treatment with the CYP17A1 inhibitor abiraterone: clinical evidence for cross-resistance? Ann Oncol. 2012;23(11):2943–7.CrossRefPubMedGoogle Scholar
  36. 36.
    Schweizer MT, Zhou XC, Wang H, Bassi S, Carducci MA, Eisenberger MA, et al. The influence of prior abiraterone treatment on the clinical activity of docetaxel in men with metastatic castration-resistant prostate cancer. Eur Urol. 2014;66(4):646–52.CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Azad AA, Leibowitz-Amit R, Eigl BJ, Lester R, Wells JC, Murray RN, et al. A retrospective, Canadian multi-center study examining the impact of prior response to abiraterone acetate on efficacy of docetaxel in metastatic castration-resistant prostate cancer. Prostate. 2014;74(15):1544–50.CrossRefPubMedGoogle Scholar
  38. 38.
    Pezaro CJ, Omlin AG, Altavilla A, Lorente D, Ferraldeschi R, Bianchini D, et al. Activity of cabazitaxel in castration-resistant prostate cancer progressing after docetaxel and next-generation endocrine agents. Eur Urol. 2014;66(3):459–65.CrossRefPubMedGoogle Scholar
  39. 39.
    Aggarwal R, Harris A, Formaker C, Small EJ, Molina A, Griffin TW, et al. Response to subsequent docetaxel in a patient cohort with metastatic castration-resistant prostate cancer after abiraterone acetate treatment. Clin Genitourin Cancer. 2014;12(5):e167–72.CrossRefPubMedGoogle Scholar
  40. 40.
    Al Nakouzi N, Le MS, Albiges L, Wang C, Beuzeboc P, Gross-Goupil M, et al. Cabazitaxel remains active in patients progressing after docetaxel followed by novel androgen receptor pathway targeted therapies. Eur Urol. 2015;68(2):228–35.CrossRefPubMedGoogle Scholar
  41. 41.
    Scher HI, Beer TM, Higano CS, Anand A, Taplin ME, Efstathiou E, et al. Antitumour activity of MDV3100 in castration-resistant prostate cancer: a phase 1-2 study. Lancet. 2010;375(9724):1437–46.CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Cassinello J, Climent MA, Del Gonzalez AA, Mellado B, Virizuela JA. SEOM clinical guidelines for the treatment of metastatic prostate cancer. Clin Transl Oncol. 2014;16(12):1060–6.CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Parker C, Gillessen S, Heidenreich A, Horwich A. Cancer of the prostate: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2015;26(Suppl 5):v69–77.CrossRefPubMedGoogle Scholar

Copyright information

© Federación de Sociedades Españolas de Oncología (FESEO) 2016

Authors and Affiliations

  • J. Cassinello
    • 1
  • J. Carballido Rodríguez
    • 2
  • L. Antón Aparicio
    • 3
  1. 1.Medical Oncology Service, Guadalajara University HospitalGuadalajaraSpain
  2. 2.Urology Service, Puerta de Hierro University HospitalMadridSpain
  3. 3.Medical Oncology Service, CHU HospitalLa Coruña, GaliciaSpain

Personalised recommendations