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:
H. A. has received personal fees from Astellas Pharma, Inc. for the submitted work and personal fees from Takeda Pharmaceutical Company Limited and Janssen Pharmaceutical K.K. outside the submitted work. Hirotsugu Uemura has received consulting fees from Astellas Pharma, Inc. for the submitted work. T. T. has received consulting fees from Astellas Pharma, Inc. S. O. has received personal fees and research funding from Astellas Pharma Inc., AstraZeneca K.K., Janssen Pharmaceutical K.K., Takeda Pharmaceutical Company Limited, and Sanofi K.K. O. O. has received consulting fees from Astellas Pharma, Inc. H. S. has received personal fees from Astellas Pharma for the submitted work; personal fees from Astellas, AstraZeneca, Takeda, and Janssen outside the submitted work; and research funds from Astellas, AstraZeneca, and Takeda outside the submitted work. M. O. has received personal fees from Astellas Pharma, Inc., Sanofi K.K., AstraZeneca K.K., ASKA Pharmaceutical, Janssen Pharmaceutical, Asahi Kasei Pharma Corp., Nippon Shinyaku Co., Nippon Kayaku Co., Kyorin Pharmaceutical, Medicon, Kissei Pharmaceutical, Shiongi & Co., Pfizer Japan, Daiichi Sankyo Co., Boston Scientific Japan K.K., Taiho Pharmaceutical Co., Novartis K.K., GSK K.K., Teijin Pharma Limited, Nihon Medi-Physics Co., Otsuka Pharmaceutical Co., Japan BCG Laboratory, Takeda Pharmaceutical, Kyowa Hakko Kirin Co., Bayer Yakuhin, and Philips Electronics Japan during the conduct of the study; research funding from AstraZeneca K.K., ASKA Pharmaceutical Co., Asahi Kasei Pharma, Nippon Shinyaku Co., Ltd, Pfizer Japan, and Takeda Pharmaceutical; and encouraged donations from Astellas Pharma, Inc., Sanofi K.K., Nippon Kayaku Co., Ltd., Kyorin Pharmaceutical Col., Ltd, Medicon, Inc., Kissei Pharmaceutical Co., Ltd., Shionogi & Co., Ltd., Daiichi Sankyo Company, Limited, Boston Scientific Japan K.K., Taiho Pharmaceutical Co., Ltd., Novartis Pharma K.K., GlaxoSmithKline K.K., Teijin Pharma Limited, Otsuka Pharmaceutical Co., Ltd, Japan BCG Laboratory, and Kyowa Hakko Kirin Co., Ltd. M. N. has received personal fees and research funding from Astellas Pharma, Inc. S. F., A. Y., and Hiroji Uemura have no conflict of interest. Y. O. has received an executive salary from Statcom, personal fees from Astellas for the submitted work; lecture fees from Daiichi Sankyo, Chugai Pharmaceutical, Shionogi, and EPS outside the submitted work; manuscript fees from Dentsu Sudler & Hennessey and DNP Media Create outside the submitted work; and research funding from Astellas for the submitted work, and research funding from Takeda Pharmaceutical, Kyowa Hakko Kirin, and Kowa Pharmaceutical outside the submitted work. H.M. is an employee of Astellas Pharma, Inc. and owns stock from Astellas. A. S. and K.T are employees of Astellas Pharma, Inc. S. N. received personal fees from Astellas during the conduct of the study and personal fees from Takeda, AstraZeneca, Janssen and GreenPeptide outside the submitted work.
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
VL - 21
SP - 773
EP - 782
JO - International Journal of Clinical Oncology
JF - International Journal of Clinical Oncology
SN - 1341-9625
IS - 4
ER -