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

Journal Article (Journal Article;Multicenter Study)

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.

Full Text

Duke Authors

Cited Authors

  • Hussain, M; Corn, PG; Michaelson, MD; Hammers, HJ; Alumkal, JJ; Ryan, CJ; Bruce, JY; Moran, S; Lee, S-Y; Lin, HM; George, DJ; Prostate Cancer Clinical Trials Consortium, a program of the Department of Defense Prostate Cancer Research Program and the Prostate Cancer Foundation,

Published Date

  • August 15, 2014

Published In

Volume / Issue

  • 20 / 16

Start / End Page

  • 4218 - 4227

PubMed ID

  • 24965748

Electronic International Standard Serial Number (EISSN)

  • 1557-3265

Digital Object Identifier (DOI)

  • 10.1158/1078-0432.CCR-14-0356


  • eng

Conference Location

  • United States