Investigational New Drugs

, Volume 30, Issue 4, pp 1652–1659

A phase II study of sorafenib in combination with bicalutamide in patients with chemotherapy-naive castration resistant prostate cancer

  • Emma K. Beardsley
  • Sebastien J. Hotte
  • Scott North
  • Susan L. Ellard
  • Eric Winquist
  • Christian Kollmannsberger
  • Som D. Mukherjee
  • Kim N. Chi
PHASE II STUDIES

DOI: 10.1007/s10637-011-9722-5

Cite this article as:
Beardsley, E.K., Hotte, S.J., North, S. et al. Invest New Drugs (2012) 30: 1652. doi:10.1007/s10637-011-9722-5

Summary

Purpose The objective of this trial was to evaluate the clinical effects of sorafenib, a multi-targeted kinase inhibitor, in combination with androgen receptor blockade in patients with castration-resistant prostate cancer. Methods This was a multicenter, two-stage, phase 2 trial. Eligible patients had rising PSA, minimal symptoms and were chemotherapy-naïve. Sorafenib 400 mg twice daily was administered with bicalutamide 50 mg once daily on a 28-day cycle. The primary endpoint was PSA response (≥50% decline) or stable disease ≥6 months. Results 39 patients were enrolled including eight without clinical evidence of metastases. Eighteen (47%) patients have had either a PSA response or stable disease ≥6 months. PSA declines of ≥50% occurred in 12 (32%) of 38 assessable patients, including seven of 27 patients (26%) with prior anti-androgen use. Median time to treatment failure was 5.5 months (95%CI = 4.8.1–8.3). Grade ≥3 adverse events included fatigue, skin rash, and hand-foot syndrome. Conclusions PSA declines and stable disease were observed with a combination of sorafenib and bicalutamide including in patients previously progressing on bicalutamide. Strategies to combine multi-targeted kinase inhibitors with hormonal therapies warrant further study in patients with CRPC.

Keywords

Phase II clinical trial Prostate cancer Sorafenib Bicalutamide 

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Emma K. Beardsley
    • 1
  • Sebastien J. Hotte
    • 2
  • Scott North
    • 3
  • Susan L. Ellard
    • 4
  • Eric Winquist
    • 5
  • Christian Kollmannsberger
    • 1
  • Som D. Mukherjee
    • 2
  • Kim N. Chi
    • 1
  1. 1.BC Cancer Agency – Vancouver Cancer CentreVancouverCanada
  2. 2.Juravinski Cancer CentreHamiltonCanada
  3. 3.Cross Cancer InstituteEdmontonCanada
  4. 4.BC Cancer Agency - Cancer Centre for the Southern InteriorKelownaCanada
  5. 5.London Health Sciences CentreLondonCanada