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.
CONCLUSIONS - 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.
ClinicalTrials. gov NCT01284920.
International journal of clinical oncology. 2016 Jan 21 [Epub ahead of print]
Hideyuki Akaza, Hirotsugu Uemura, Taiji Tsukamoto, Seiichiro Ozono, Osamu Ogawa, Hideki Sakai, Mototsugu Oya, Mikio Namiki, Satoshi Fukasawa, Akito Yamaguchi, Hiroji Uemura, Yasuo Ohashi, Hideki Maeda, Atsushi Saito, Kentaro Takeda, Seiji Naito
Strategic Investigation On Comprehensive Cancer Network, The University of Tokyo, 4-6-1 Komaba, Meguro-ku, Tokyo, 153-8904, Japan. Department of Urology, Kinki University Faculty of Medicine, 377-2 Ono-Higashi, Osakasayama, 589-8511, Japan. , Department of Urology, Sapporo Medical University School of Medicine, S1 W17 Chuo-ku, Sapporo, 060-8556, Japan. , Department of Urology, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, 431-3192, Japan. , Department of Urology, Kyoto University Graduate School of Medicine, Yoshida-Konoe-cho, Sakyo-ku, Kyoto, 606-8501, Japan. , Department of Urology, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan. , Department of Urology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan. , Department of Integrative Cancer Therapy and Urology, Kanazawa University Graduate School of Medical Sciences, 13-1 Takara-machi, Kanazawa, 920-8641, Japan. , Department of Urology, Chiba Cancer Center, 666-2 Nitona-Cho, Chuo-ku, Chiba, 260-8717, Japan. , Division of Urology, Harasanshin Hospital, 1-8 Taihakumachi, Hakata-ku, Fukuoka, 812-0033, Japan. , Department of Urology and Renal Transplantation, Yokohama City University Medical Center, 4-57 Urafune, Minami-ku, Yokohama, 232-0024, Japan. , Department of Integrated Science and Engineering for Sustainable Society, Chuo University, 1-13-27 Kasuga, Bunkyo-ku, Tokyo, 112-8551, Japan. , Astellas Pharma Inc, 2-5-1 Nihonbashi-Honcho, Chuo-Ku, Tokyo, 103-8411, Japan. , Astellas Pharma Inc, 2-5-1 Nihonbashi-Honcho, Chuo-Ku, Tokyo, 103-8411, Japan. , Astellas Pharma Inc, 2-5-1 Nihonbashi-Honcho, Chuo-Ku, Tokyo, 103-8411, Japan. , Division of Urology, Harasanshin Hospital, 1-8 Taihakumachi, Hakata-ku, Fukuoka, 812-0033, Japan.