Advertisement

Enzalutamide versus flutamide for castration-resistant prostate cancer after combined androgen blockade therapy with bicalutamide: a retrospective study

  • Taro IguchiEmail author
  • Satoshi Tamada
  • Minoru Kato
  • Sayaka Yasuda
  • Taiyo Otoshi
  • Kosuke Hamada
  • Takeshi Yamasaki
  • Tatsuya Nakatani
Original Article
  • 3 Downloads

Abstract

Background

Alternative anti-androgen therapy (AAT) with flutamide after combined androgen blockade (CAB) therapy with bicalutamide for metastatic prostate cancer is common. However, no studies have compared enzalutamide without AAT with enzalutamide after AAT with flutamide as treatment for castration-resistant prostate cancer (CRPC). We aimed to compare the efficacies of flutamide and enzalutamide for CRPC.

Methods

In our hospital, 55 patients were diagnosed with CRPC after CAB therapy and administered flutamide or enzalutamide between May 2014 and December 2017. Patients with flutamide failure were administered enzalutamide. We evaluated the (1) prostate-specific antigen (PSA) best response with initial therapy, (2) PSA progression-free survival with initial therapy (PSA-PFS), (3) PSA best response with enzalutamide therapy, (4) PSA-PFS of enzalutamide therapy, and (5) overall survival (OS).

Results

As first-line therapy, patients were administered enzalutamide (n = 29) or flutamide (n = 26). In the flutamide group, 18 patients showed disease progression and were administered enzalutamide. PSA best response was statistically higher in the enzalutamide group. PSA-PFS was significantly longer in the enzalutamide group [hazard ratio (HR) 0.42, 95% confidence interval (CI) 0.19–0.92, p = 0.024]. However, there was no significant difference in PSA best response with enzalutamide therapy and PSA-PFS between the first- and second-line enzalutamide therapies (HR 0.80, 95% CI 0.33–1.94, p = 0.62). There was no significant difference in OS between enzalutamide and flutamide groups (HR 1.85, 95% CI 0.53–6.42, p = 0.33).

Conclusions

AAT with subsequent flutamide after CAB therapy with bicalutamide may be suitable for some CRPC patients.

Keywords

Castration-resistant prostate cancer Enzalutamide Flutamide 

Notes

Acknowledgements

The authors wish to thank the following collaborators for help with patient care: Dr. Katsuyuki Kuratsukuri, Dr. Nobuyuki Kuwabara, and Dr. Tomoaki Iwai.

Compliance with ethical standards

Conflict of interest

Taro Iguchi, Sayaka Yasuda, and Tatsuya Nakatani received a research grant from Astellas Pharma Inc. and Bayer Yakuhin, Ltd.; Taro Iguchi received lecture fees from Astellas Pharma Inc., Bayer Yakuhin, Ltd. Janssen Pharmaceutical K.K., and Sanofi K.K.; Satoshi Tamada, Minoru Kato, Taiyo Otoshi, Kosuke Hamada, and Takeshi Yamasaki have no conflict of interest.

References

  1. 1.
    Siegel RL, Miller KD, Jemal A (2018) Cancer statistics, 2018. CA Cancer J Clin 68(1):7–30.  https://doi.org/10.3322/caac.21442 CrossRefGoogle Scholar
  2. 2.
    Akaza H, Hinotsu S, Usami M et al (2009) Combined androgen blockade with bicalutamide for advanced prostate cancer: long-term follow-up of a phase 3, double-blind, randomized study for survival. Cancer 115(15):3437–3445.  https://doi.org/10.1002/cncr.24395 CrossRefGoogle Scholar
  3. 3.
    Fujikawa K, Matsui Y, Fukuzawa S et al (2000) Prostate-specific antigen levels and clinical response to flutamide as the second hormone therapy for hormone-refractory prostate carcinoma. Eur Urol 37(2):218–222.  https://doi.org/10.1159/000020121 CrossRefGoogle Scholar
  4. 4.
    Miyake H, Hara I, Eto H (2005) Clinical outcome of maximum androgen blockade using flutamide as second-line hormonal therapy for hormone-refractory prostate cancer. BJU Int 96(6):791–795.  https://doi.org/10.1111/j.1464-410X.2005.05766.x CrossRefGoogle Scholar
  5. 5.
    Okihara K, Ukimura O, Kanemitsu N et al (2007) Clinical efficacy of alternative antiandrogen therapy in Japanese men with relapsed prostate cancer after first-line hormonal therapy. Int J Urol 14(2):128–132.  https://doi.org/10.1111/j.1442-2042.2007.01698.x CrossRefGoogle Scholar
  6. 6.
    Nishimura K, Arichi N, Tokugawa S et al (2007) Effects of flutamide as a second-line agent for maximum androgen blockade of hormone refractory prostate cancer. Int J Urol 14(3):264–267.  https://doi.org/10.1111/j.1442-2042.2007.01681.x CrossRefGoogle Scholar
  7. 7.
    Suzuki H, Okihara K, Miyake H et al (2008) Alternative nonsteroidal antiandrogen therapy for advanced prostate cancer that relapsed after initial maximum androgen blockade. J Urol 180(3):921–927.  https://doi.org/10.1016/j.juro.2008.05.045 CrossRefGoogle Scholar
  8. 8.
    Okegawa T, Nutahara K, Higashihara E (2010) Alternative antiandrogen therapy in patients with castration-resistant prostate cancer: a single-center experience. Int J Urol 17(11):950–955.  https://doi.org/10.1111/j.1442-2042.2010.02620.x CrossRefGoogle Scholar
  9. 9.
    Yasui M, Uemura K, Yoneyama S et al (2016) Predictors of poor response to secondary alternative antiandrogen therapy with flutamide in metastatic castration-resistant prostate cancer. Jpn J Clin Oncol 46(11):1042–1046.  https://doi.org/10.1093/jjco/hyw110 CrossRefGoogle Scholar
  10. 10.
    Lowrance WT, Roth BJ, Kirkby E et al (2016) Castration-resistant prostate cancer: AUA guideline amendment 2015. J Urol 195(5):1444–1452.  https://doi.org/10.1016/j.juro.2015.10.086 CrossRefGoogle Scholar
  11. 11.
    Tran C, Ouk S, Clegg NJ et al (2009) Development of a second-generation antiandrogen for treatment of advanced prostate cancer. Science 324(5928):787–790.  https://doi.org/10.1126/science.1168175 CrossRefGoogle Scholar
  12. 12.
    Jung ME, Ouk S, Yoo D et al (2010) Structure-activity relationship for thiohydantoin androgen receptor antagonists for castration-resistant prostate cancer (CRPC). J Med Chem 53(7):2779–2796.  https://doi.org/10.1021/jm901488g CrossRefGoogle Scholar
  13. 13.
    Scher HI, Fizazi K, Saad F et al (2012) Increased survival with enzalutamide in prostate cancer after chemotherapy. N Engl J Med 367(13):1187–1197.  https://doi.org/10.1056/NEJMoa1207506 CrossRefGoogle Scholar
  14. 14.
    Beer TM, Armstrong AJ, Rathkopf DE et al (2014) Enzalutamide in metastatic prostate cancer before chemotherapy. N Engl J Med 371(5):424–433.  https://doi.org/10.1056/NEJMoa1405095 CrossRefGoogle Scholar
  15. 15.
    Kim CS, Choi YD, Lee SE et al (2017) Post hoc analyses of East Asian patients from the randomized placebo-controlled PREVAIL trial of enzalutamide in patients with chemotherapy-naive, metastatic castration-resistant prostate cancer. Medicine 96(27):e7223.  https://doi.org/10.1097/md.0000000000007223 CrossRefGoogle Scholar
  16. 16.
    Kimura G, Yonese J, Fukagai T et al (2016) Enzalutamide in Japanese patients with chemotherapy-naive, metastatic castration-resistant prostate cancer: A post-hoc analysis of the placebo-controlled PREVAIL trial. Int J Urol 23(5):395–403.  https://doi.org/10.1111/iju.13072 CrossRefGoogle Scholar
  17. 17.
    Scher HI, Halabi S, Tannock I et al (2008) Design and end points of clinical trials for patients with progressive prostate cancer and castrate levels of testosterone: recommendations of the Prostate Cancer Clinical Trials Working Group. J Clin Oncol 26(7):1148–1159.  https://doi.org/10.1200/JCO.2007.12.4487 CrossRefGoogle Scholar
  18. 18.
    Eisenberger MA, Blumenstein BA, Crawford ED et al (1998) Bilateral orchiectomy with or without flutamide for metastatic prostate cancer. N Engl J Med 339(15):1036–1042.  https://doi.org/10.1056/nejm199810083391504 CrossRefGoogle Scholar
  19. 19.
    Momozono H, Miyake H, Tei H et al (2016) Clinical outcomes of anti-androgen withdrawal and subsequent alternative anti-androgen therapy for advanced prostate cancer following failure of initial maximum androgen blockade. Mol Clin Oncol 4(5):839–844.  https://doi.org/10.3892/mco.2016.817 CrossRefGoogle Scholar
  20. 20.
    Penson DF, Armstrong AJ, Concepcion R et al (2016) Enzalutamide versus bicalutamide in castration-resistant prostate cancer: the STRIVE trial. J Clin Oncol 34(18):2098–2106.  https://doi.org/10.1200/jco.2015.64.9285 CrossRefGoogle Scholar
  21. 21.
    Shore ND, Chowdhury S, Villers A et al (2016) Efficacy and safety of enzalutamide versus bicalutamide for patients with metastatic prostate cancer (TERRAIN): a randomised, double-blind, phase 2 study. Lancet Oncol 17(2):153–163.  https://doi.org/10.1016/s1470-2045(15)00518-5 CrossRefGoogle Scholar
  22. 22.
    Kamiya N, Suzuki H, Nishimura K et al (2014) Development of nomogram to non-steroidal antiandrogen sequential alternation in prostate cancer for predictive model. Jpn J Clin Oncol 44(3):263–269.  https://doi.org/10.1093/jjco/hyt230 CrossRefGoogle Scholar
  23. 23.
    Nagai T, Naiki T, Iida K et al (2018) Early abiraterone acetate treatment is beneficial in Japanese castration-resistant prostate cancer after failure of primary combined androgen blockade. Prostate Int 6(1):18–23.  https://doi.org/10.1016/j.prnil.2017.07.001 CrossRefGoogle Scholar
  24. 24.
    Zhao JG, Liu JD, Shen PF et al (2018) Prior switching to a second-line nonsteroidal antiandrogen does not impact the therapeutic efficacy of abiraterone acetate in patients with metastatic castration-resistant prostate cancer: a real-world retrospective study. Asian J Androl 20(6):545–550.  https://doi.org/10.4103/aja.aja_58_18 CrossRefGoogle Scholar
  25. 25.
    Fizazi K, Tran N, Fein L et al (2017) Abiraterone plus prednisone in metastatic, castration-sensitive prostate cancer. N Engl J Med 377(4):352–360.  https://doi.org/10.1056/NEJMoa1704174 CrossRefGoogle Scholar
  26. 26.
    James ND, de Bono JS, Spears MR et al (2017) Abiraterone for prostate cancer not previously treated with hormone therapy. N Engl J Med 377(4):338–351.  https://doi.org/10.1056/NEJMoa1702900 CrossRefGoogle Scholar
  27. 27.
    Sweeney CJ, Chen YH, Carducci M et al (2015) Chemohormonal therapy in metastatic hormone-sensitive prostate cancer. N Engl J Med 373(8):737–746.  https://doi.org/10.1056/NEJMoa1503747 CrossRefGoogle Scholar

Copyright information

© Japan Society of Clinical Oncology 2019

Authors and Affiliations

  1. 1.Department of UrologyOsaka City University Graduate School of MedicineOsakaJapan

Personalised recommendations