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

Publication ,  Journal Article
Hussain, M; Corn, PG; Michaelson, MD; Hammers, HJ; Alumkal, JJ; Ryan, CJ; Bruce, JY; Moran, S; Lee, S-Y; Lin, HM; George, DJ ...
Published in: Clin Cancer Res
August 15, 2014

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.

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Published In

Clin Cancer Res

DOI

EISSN

1557-3265

Publication Date

August 15, 2014

Volume

20

Issue

16

Start / End Page

4218 / 4227

Location

United States

Related Subject Headings

  • Time Factors
  • Survival Rate
  • Steroid 17-alpha-Hydroxylase
  • Prostatic Neoplasms, Castration-Resistant
  • Prostate-Specific Antigen
  • Prognosis
  • Oncology & Carcinogenesis
  • Neoplasm Staging
  • Neoplasm Grading
  • Naphthalenes
 

Citation

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Hussain, M., Corn, P. G., Michaelson, M. D., Hammers, H. J., Alumkal, J. J., Ryan, C. J., … Prostate Cancer Clinical Trials Consortium, a program of the Department of Defense Prostate Cancer Research Program and the Prostate Cancer Foundation, . (2014). 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, 20(16), 4218–4227. https://doi.org/10.1158/1078-0432.CCR-14-0356
Hussain, Maha, Paul G. Corn, M Dror Michaelson, Hans J. Hammers, Joshi J. Alumkal, Charles J. Ryan, Justine Y. Bruce, et al. “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 20, no. 16 (August 15, 2014): 4218–27. https://doi.org/10.1158/1078-0432.CCR-14-0356.
Hussain M, Corn PG, Michaelson MD, Hammers HJ, Alumkal JJ, Ryan CJ, et al. 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.
Hussain, Maha, et al. “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, vol. 20, no. 16, Aug. 2014, pp. 4218–27. Pubmed, doi:10.1158/1078-0432.CCR-14-0356.
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. 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):4218–4227.

Published In

Clin Cancer Res

DOI

EISSN

1557-3265

Publication Date

August 15, 2014

Volume

20

Issue

16

Start / End Page

4218 / 4227

Location

United States

Related Subject Headings

  • Time Factors
  • Survival Rate
  • Steroid 17-alpha-Hydroxylase
  • Prostatic Neoplasms, Castration-Resistant
  • Prostate-Specific Antigen
  • Prognosis
  • Oncology & Carcinogenesis
  • Neoplasm Staging
  • Neoplasm Grading
  • Naphthalenes