A multicenter phase I/II study of enzalutamide in Japanese patients with castration-resistant prostate cancer.
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.
['Akaza|Hideyuki|H|', 'Uemura|Hirotsugu|H|', 'Tsukamoto|Taiji|T|', 'Ozono|Seiichiro|S|', 'Ogawa|Osamu|O|', 'Sakai|Hideki|H|', 'Oya|Mototsugu|M|', 'Namiki|Mikio|M|', 'Fukasawa|Satoshi|S|', 'Yamaguchi|Akito|A|', 'Uemura|Hiroji|H|', 'Ohashi|Yasuo|Y|', 'Maeda|Hideki|H|', 'Saito|Atsushi|A|', 'Takeda|Kentaro|K|', 'Naito|Seiji|S|']
D000368:Aged D000369:Aged, 80 and over D000970:Antineoplastic Agents D044466:Asians D001549:Benzamides D014408:Biomarkers, Tumor D004334:Drug Administration Schedule D006801:Humans D007564:Japan D008297:Male D008875:Middle Aged D060787:Neoplasm Grading D009367:Neoplasm Staging D009570:Nitriles D010669:Phenylthiohydantoin D017430:Prostate-Specific Antigen D064129:Prostatic Neoplasms, Castration-Resistant D016896:Treatment Outcome
Enzalutamide Androgen receptor inhibitor Metastatic castration-resistant prostate cancer