TY - JOUR
T1 - A multicenter phase I/II study of enzalutamide in Japanese patients with castration-resistant prostate cancer
AU - Akaza, Hideyuki
AU - Uemura, Hirotsugu
AU - Tsukamoto, Taiji
AU - Ozono, Seiichiro
AU - Ogawa, Osamu
AU - Sakai, Hideki
AU - Oya, Mototsugu
AU - Namiki, Mikio
AU - Fukasawa, Satoshi
AU - Yamaguchi, Akito
AU - Uemura, Hiroji
AU - Ohashi, Yasuo
AU - Maeda, Hideki
AU - Saito, Atsushi
AU - Takeda, Kentaro
AU - Naito, Seiji
N1 - Funding Information:
We thank the patients in the study for their cooperation, along with the following investigators: Hiroshi Kitamura, Sapporo Medical University Hospital; Hideo Saito, Tohoku University Hospital; Senji Hoshi, Yamagata Prefectural Central Hospital; Kazuhiro Suzuki, Gunma University Hospital; Takeshi Ueda, Chiba Cancer Center; Tomohiko Ichikawa, Chiba University Hospital; Yataro Yamanaka, Nihon University Itabashi Hospital; Takashi Fukagai, Showa University Hospital; Hirohiko Nagata, Keio University Hospital; Hiroyuki Fujimoto, National Cancer Center Hospital; Shin Egawa, Jikei University Hospital; Takatsugu Okegawa, Kyorin University Hospital; Hiroji Uemura, Yokohama City University Hospital; Tsutomu Nishiyama, Niigata University Medical and Dental Hospital; Atsushi Mizokami, Kanazawa University Hospital; Tatsuya Takayama, Hamamatsu University Hospital; Takahiro Inoue, Kyoto University Hospital; Tatsuya Nakatani, Osaka City University Hospital; Kazuo Nishimura, Osaka Medical Center for Cancer and Cardiovascular Diseases; Norio Nonomura, Osaka University Hospital; Masahiro Nozawa, Kinki University Hospital; Sadanori Kamikawa, Osaka City General Hospital; Tomoharu Fukumori, Tokushima University Hospital; Shigeru Sakano, Yamaguchi University Hospital; Akito Yamaguchi, Harasanshin Hospital; Akira Yokomizo, Kyushu University Hospital; Tsukasa Igawa, Nagasaki University Hospital. We also thank the following independent data monitoring committee and independent RECIST assessment committee members: Shigeo Horie, Juntendo University Graduate School of Medicine; Shiro Hinotsu, Okayama University Hospital; Kojiro Yamamoto, Gunma University; Koichiro Akakura, Tokyo Shinjuku Medical Center; Yuichi Watanabe, National Cancer Center Hospital. Enzalutamide is being co-developed by Medivation, Inc, and Astellas Pharma, Inc. This study was funded by Astellas Pharma, Inc. The authors would like to thank Lauren Smith of Complete HealthVizion for copyediting the manuscript, which was funded by Astellas Pharma, Inc and Medivation, Inc.
Publisher Copyright:
© 2016, The Author(s).
PY - 2016/8/1
Y1 - 2016/8/1
N2 - Background: The safety, tolerability, pharmacokinetics (PK) and anti-tumor activity of enzalutamide were investigated in patients with castration-resistant prostate cancer (CRPC) in Japan through a multicenter phase I/II study. Methods: In phase I, patients with progressive metastatic CRPC received single, then multiple, ascending doses of enzalutamide 80, 160 or 240 mg/day. After assessment of tolerability at multiple doses of 160 mg/day for 4 weeks, post-docetaxel patients with CRPC and measurable disease were enrolled into phase II; receiving long-term administration of enzalutamide 160 mg/day. Results: Nine and 38 patients were enrolled in phase I and II, respectively. During phase I, enzalutamide was well tolerated in each cohort; PK parameters were similar to those of non-Japanese populations in other studies. By week 12, overall response rate was 5.3 % and clinical benefit rate was 47.4 %. Prostate-specific antigen response rate (≥50 % reduction from baseline) was 28.9 %. Treatment-emergent adverse events reported in >20 % of patients in phase II were decreased weight, decreased appetite and constipation. No seizures were observed. Conclusion: Enzalutamide at 160 mg/day was well tolerated, with PK and safety profiles similar to the non-Japanese population. Anti-tumor activity was observed in post-docetaxel Japanese patients with metastatic CRPC. Apparent differences in anti-tumor activity compared with the AFFIRM study (a phase III trial in a diverse population of patients with CRPC post-docetaxel) may be attributed to differences in treatment history prior to starting enzalutamide. Particularly in Japan, the influence of sequence in hormone treatments, including combined androgen blockade therapy, should be considered. Trial registration: ClinicalTrials.gov NCT01284920.
AB - Background: The safety, tolerability, pharmacokinetics (PK) and anti-tumor activity of enzalutamide were investigated in patients with castration-resistant prostate cancer (CRPC) in Japan through a multicenter phase I/II study. Methods: In phase I, patients with progressive metastatic CRPC received single, then multiple, ascending doses of enzalutamide 80, 160 or 240 mg/day. After assessment of tolerability at multiple doses of 160 mg/day for 4 weeks, post-docetaxel patients with CRPC and measurable disease were enrolled into phase II; receiving long-term administration of enzalutamide 160 mg/day. Results: Nine and 38 patients were enrolled in phase I and II, respectively. During phase I, enzalutamide was well tolerated in each cohort; PK parameters were similar to those of non-Japanese populations in other studies. By week 12, overall response rate was 5.3 % and clinical benefit rate was 47.4 %. Prostate-specific antigen response rate (≥50 % reduction from baseline) was 28.9 %. Treatment-emergent adverse events reported in >20 % of patients in phase II were decreased weight, decreased appetite and constipation. No seizures were observed. Conclusion: Enzalutamide at 160 mg/day was well tolerated, with PK and safety profiles similar to the non-Japanese population. Anti-tumor activity was observed in post-docetaxel Japanese patients with metastatic CRPC. Apparent differences in anti-tumor activity compared with the AFFIRM study (a phase III trial in a diverse population of patients with CRPC post-docetaxel) may be attributed to differences in treatment history prior to starting enzalutamide. Particularly in Japan, the influence of sequence in hormone treatments, including combined androgen blockade therapy, should be considered. Trial registration: ClinicalTrials.gov NCT01284920.
KW - Androgen receptor inhibitor
KW - Enzalutamide
KW - Metastatic castration-resistant prostate cancer
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U2 - 10.1007/s10147-016-0952-6
DO - 10.1007/s10147-016-0952-6
M3 - Article
C2 - 26793974
AN - SCOPUS:84955312461
SN - 1341-9625
VL - 21
SP - 773
EP - 782
JO - International Journal of Clinical Oncology
JF - International Journal of Clinical Oncology
IS - 4
ER -