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Factors predicting efficacy and adverse effects of enzalutamide in Japanese patients with castration-resistant prostate cancer: results of retrospective multi-institutional study

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Abstract

Background

We aimed to evaluate the factors predicting efficacy and adverse effects of enzalutamide in patients with castration-resistant prostate cancer.

Methods

We retrospectively evaluated data on 345 patients who had received enzalutamide for castration-resistant prostate cancer in 20 hospitals (Kyoto University Hospital and other satellite hospitals). Cox proportional hazards regression analysis was performed to identify factors predicting prostate-specific antigen (PSA) progression after enzalutamide treatment and logistic regression analysis for those associated with development of adverse effects.

Results

PSA titers decreased by >50 % in 197 patients (57 %). The median PSA progression free survival was 163 days. Gleason score >8 (HR 2.078, 95 % CI 1.37–3.153, P = 0.00058), performance status ≥1 (HR 2.292, 95 % CI 1.463–3.592, P = 0.000296), presence of bone metastasis (HR 1.774, 95 % CI 1.019–3.090, P = 0.0429), visceral metastasis (HR 2.127, 95 % CI 1.215–3.722, P = 0.00823), previous steroid treatment (HR 1.780, 95 % CI 1.207–2.626, P = 0.00361) and docetaxel treatment (HR 1.602, 95 % CI 1.051–2.442, P = 0.0284) significantly predicted the efficacy of enzalutamide. Adverse effects, including fatigue or appetite loss, occurred in 169 patients (49 %), 48 (18 %) of whom stopped enzalutamide. Age >75 years (HR 1.980, 95 % CI 1.270–3.09, P = 0.00246) and lower enzalutamide dose (HR 0.437, 95 % CI 0.255–1.270, P = 0.00249) were significantly associated with development of adverse effects.

Conclusions

Enzalutamide treatment is effective in patients with castration-resistant prostate cancer with low Gleason scores, good performance status, without bone or visceral metastasis and no prior steroid or docetaxel treatment. Lower doses of enzalutamide decrease the incidence of adverse effects, especially in older patients.

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References

  1. Siegel R, Ma J, Zou Z et al (2014) Cancer statistics. CA Cancer J Clin 64(1):9–29. doi:10.3322/caac.21208

    Article  PubMed  Google Scholar 

  2. Ito K (2014) Prostate cancer in Asian men. Nat Rev Urol 11(4):197–212. doi:10.1038/nrurol.2014.42

    Article  PubMed  Google Scholar 

  3. Harris WP, Mostaghel EA, Nelson PS et al (2009) Androgen deprivation therapy: progress in understanding mechanisms of resistance and optimizing androgen depletion. Nat Clin Pract Urol 6(2):76–85. doi:10.1038/ncpuro1296

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Tannock IF, de Wit R, Berry WR et al (2004) Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. N Engl J Med 351(15):1502–1512. doi:10.1056/NEJMoa040720

    Article  CAS  PubMed  Google Scholar 

  5. Armstrong AJ, Eisenberger MA, Halabi S et al (2012) Biomarkers in the management and treatment of men with metastatic castration-resistant prostate cancer. Eur Urol 61(3):549–559. doi:10.1016/j.eururo.2011.11.009

    Article  CAS  PubMed  Google Scholar 

  6. 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. doi:10.1056/NEJMoa1207506

    Article  CAS  PubMed  Google Scholar 

  7. Beer TM, Tombal B (2014) Enzalutamide in metastatic prostate cancer before chemotherapy. N Engl J Med 371(18):1755–1756. doi:10.1056/NEJMc1410239

    Article  PubMed  Google Scholar 

  8. Antonarakis ES, Lu C, Wang H et al (2014) AR-V7 and resistance to enzalutamide and abiraterone in prostate cancer. N Engl J Med 371(11):1028–1038. doi:10.1056/NEJMoa1315815

    Article  PubMed  PubMed Central  Google Scholar 

  9. Goodman OB Jr, Flaig TW, Molina A et al (2014) Exploratory analysis of the visceral disease subgroup in a phase III study of abiraterone acetate in metastatic castration-resistant prostate cancer. Prostate Cancer Prostatic Dis 17(1):34–39. doi:10.1038/pcan.2013.41

    Article  CAS  PubMed  Google Scholar 

  10. Ryan CJ, Molina A, Li J et al (2013) Serum androgens as prognostic biomarkers in castration-resistant prostate cancer: results from an analysis of a randomized phase III trial. J Clin Oncol 31(22):2791–2798. doi:10.1200/JCO.2012.45.4595

    Article  CAS  PubMed  Google Scholar 

  11. Arora VK, Schenkein E, Murali R et al (2013) Glucocorticoid receptor confers resistance to antiandrogens by bypassing androgen receptor blockade. Cell 155(6):1309–1322. doi:10.1016/j.cell.2013.11.012

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Narayanan S, Srinivas S, Feldman D (2015) Androgen-glucocorticoid interactions in the era of novel prostate cancer therapy. Nat Rev Urol. doi:10.1038/nrurol.2015.254

    PubMed  Google Scholar 

Download references

Acknowledgments

The authors wish to acknowledge the assistance of the following in this study: Takehiko Segawa, Toru Yoshida, Kyoto City Hospital; Hiroshi Okuno, Kyoto Medical Center; Mitsuo Nonomura, Norio Kawase, Kyoto Katsura Hospital; ** Yamada, Toru Kanno, I**kai Takeda Hospital; Tomoyuki Oida, Kosekai Takeda Hospital; Toshiya Akao, Noboru Shibasaki, Otowa Hospital; Keiji Ogura, Toru Isitoya, Otsu Red Cross Hospital; Yasumasa Shichiri, Akihiro Hamada, Otsu Municipal Hospital; Hiroyuki Onishi, Koji Nishizawa, Shiga Medical Center for Adults; Kazuo Nishimura, Kazutoshi Okubo, Osaka Red Cross Hospital; Jun Takenawa, Takatsuki Red Cross Hospital; Hiroshi Kanamaru, Takeshi Soda, Kitano Hospital; Takayuki Hashimura, Kaoru Murakami, Kansai Electric Power Hospital; Mutsushi Kawakita, Takashi Matsuoka, Kobe City Medical Center General Hospital; Noriyuki Ito, Yosuke Shimizu, Nishikobe Medical Center; Yoji Taki, Jun Watanabe, Toyoka Public Hospital; Hiroshi Iwamura, Ayumu Matsuda, Hmeji Medical Center; Kazuhiro Okumura, Hiroaki Kawanishi, Tenri Hospital; and Tadashi Hayashi, Masahiro Tamaki, Japanese Red Cross Society Wakayama Medical Center.

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Authors and Affiliations

  1. Department of Urology, Kyoto University Graduate School of Medicine, 54 Shogoinkawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan

    Naoki Terada, Shusuke Akamatsu, Yoshiyuki Okada, Hiromitsu Negoro, Takashi Kobayashi, Toshinari Yamasaki, Yoshiyuki Matsui, Takahiro Inoue, Tomomi Kamba & Osamu Ogawa

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  1. Naoki Terada
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  2. Shusuke Akamatsu
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  3. Yoshiyuki Okada
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  9. Tomomi Kamba
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  10. Osamu Ogawa
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Correspondence to Osamu Ogawa.

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Terada, N., Akamatsu, S., Okada, Y. et al. Factors predicting efficacy and adverse effects of enzalutamide in Japanese patients with castration-resistant prostate cancer: results of retrospective multi-institutional study. Int J Clin Oncol 21, 1155–1161 (2016). https://doi.org/10.1007/s10147-016-1004-y

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  • DOI: https://doi.org/10.1007/s10147-016-1004-y

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