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International Journal of Clinical Oncology
Published in: International Journal of Clinical Oncology 4/2016

Open Access 01-08-2016 | Original Article

A multicenter phase I/II study of enzalutamide in Japanese patients with castration-resistant prostate cancer

Authors: 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

Published in: International Journal of Clinical Oncology | Issue 4/2016

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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.
Appendix
Available only for authorised users
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Metadata
Title
A multicenter phase I/II study of enzalutamide in Japanese patients with castration-resistant prostate cancer
Authors
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
Publication date
01-08-2016
Publisher
Springer Japan
Published in
International Journal of Clinical Oncology / Issue 4/2016
Print ISSN: 1341-9625
Electronic ISSN: 1437-7772
DOI
https://doi.org/10.1007/s10147-016-0952-6

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