PURPOSE: Orteronel (TAK-700) is an investigational, nonsteroidal, oral, 
inhibitor of androgen synthesis with greater specificity for 17,20-lyase than 
for 17α-hydroxylase. We investigated orteronel without steroids in patients with 
nonmetastatic castration-resistant prostate cancer (nmCRPC; M0).
EXPERIMENTAL DESIGN: Patients with nmCRPC and rising prostate-specific antigen 
(PSA) received orteronel 300 mg twice daily until PSA progression, metastases, 
or unacceptable toxicity. The primary endpoint was percentage of patients 
achieving PSA ≤0.2 ng/mL (undetectable levels) at 3 months. Secondary endpoints 
included safety, PSA response, time to metastases, and correlated endpoints.
RESULTS: Thirty-nine patients with a median baseline PSA doubling time of 2.4 
months (range, 0.9-9.2) received a median of fourteen 28-day treatment cycles. 
PSA decreased >30% in 35 patients and 6 (16%) achieved PSA ≤ 0.2 ng/mL at 3 
months. Median times to PSA progression and metastasis were 13.8 and 25.4 
months, respectively. Kaplan-Meier estimates of freedom from PSA progression 
were 57% and 42% at 12 and 24 months, and of freedom from metastasis were 94% 
and 62% at 12 and 24 months, respectively. At 3 months, median testosterone 
declined by 89% from baseline. Adverse events led to therapy discontinuation in 
12 patients and grade ≥3/4 adverse events occurred in 22 patients. Most frequent 
all-cause adverse events included fatigue (64%), hypertension (44%), diarrhea 
(38%), and nausea (33%), which were primarily grade 1/2.
CONCLUSIONS: Single-agent orteronel produced marked and durable declines in PSA 
in patients with nmCRPC. Orteronel has moderate but manageable toxicities and 
its chronic administration without steroids appears feasible.