Phase II study of single-agent orteronel (TAK-700) in patients with nonmetastatic castration-resistant prostate cancer and rising prostate-specific antigen

Clin Cancer Res. 2014 Aug 15;20(16):4218-27. doi: 10.1158/1078-0432.CCR-14-0356. Epub 2014 Jun 25.


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.

Trial registration: NCT01046916.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / blood*
  • Bone Density / drug effects
  • Disease Progression
  • Follow-Up Studies
  • Humans
  • Imidazoles / therapeutic use*
  • Male
  • Middle Aged
  • Naphthalenes / therapeutic use*
  • Neoplasm Grading
  • Neoplasm Staging
  • Prognosis
  • Prostate-Specific Antigen / blood*
  • Prostatic Neoplasms, Castration-Resistant / drug therapy*
  • Steroid 17-alpha-Hydroxylase / antagonists & inhibitors*
  • Survival Rate
  • Time Factors


  • Biomarkers, Tumor
  • Imidazoles
  • Naphthalenes
  • Steroid 17-alpha-Hydroxylase
  • Prostate-Specific Antigen
  • orteronel

Associated data