Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 1-10 |
| Number of pages | 10 |
| Journal | International Journal of Clinical Oncology |
| DOIs | |
| Publication status | Accepted/In press - 2016 Jan 21 |
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Keywords
- Androgen receptor inhibitor
- Enzalutamide
- Metastatic castration-resistant prostate cancer
ASJC Scopus subject areas
- Oncology
- Surgery
- Hematology
Cite this
A multicenter phase I/II study of enzalutamide in Japanese patients with castration-resistant prostate cancer. / Akaza, Hideyuki; Uemura, Hirotsugu; Tsukamoto, Taiji; Ozono, Seiichiro; Ogawa, Osamu; Sakai, Hideki; Oya, Mototsugu; Namiki, Mikio; Fukasawa, Satoshi; Yamaguchi, Akito; Uemura, Hiroji; Ohashi, Yasuo; Maeda, Hideki; Saito, Atsushi; Takeda, Kentaro; Naito, Seiji.
In: International Journal of Clinical Oncology, 21.01.2016, p. 1-10.Research output: Contribution to journal › Article
}
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
PY - 2016/1/21
Y1 - 2016/1/21
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
UR - http://www.scopus.com/inward/record.url?scp=84955312461&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84955312461&partnerID=8YFLogxK
U2 - 10.1007/s10147-016-0952-6
DO - 10.1007/s10147-016-0952-6
M3 - Article
C2 - 26793974
AN - SCOPUS:84955312461
SP - 1
EP - 10
JO - International Journal of Clinical Oncology
JF - International Journal of Clinical Oncology
SN - 1341-9625
ER -