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

  • PHASE II STUDIES
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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.

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Acknowledgements

This work was supported by a grant-in-aid from Bayer Inc.

Study management was performed by Ozmosis Research Inc.

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Authors and Affiliations

  1. BC Cancer Agency – Vancouver Cancer Centre, 600 West 10th Avenue, Vancouver, British Columbia, Canada, V5Z 4E6

    Emma K. Beardsley, Christian Kollmannsberger & Kim N. Chi

  2. Juravinski Cancer Centre, Hamilton, Canada

    Sebastien J. Hotte & Som D. Mukherjee

  3. Cross Cancer Institute, Edmonton, Canada

    Scott North

  4. BC Cancer Agency - Cancer Centre for the Southern Interior, Kelowna, Canada

    Susan L. Ellard

  5. London Health Sciences Centre, London, Canada

    Eric Winquist

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  1. Emma K. Beardsley
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  2. Sebastien J. Hotte
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Correspondence to Kim N. Chi.

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Beardsley, E.K., Hotte, S.J., North, S. et al. A phase II study of sorafenib in combination with bicalutamide in patients with chemotherapy-naive castration resistant prostate cancer. Invest New Drugs 30, 1652–1659 (2012). https://doi.org/10.1007/s10637-011-9722-5

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  • DOI: https://doi.org/10.1007/s10637-011-9722-5

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