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

Author： Beardsley Emma

Publisher： Springer Publishing Company

ISSN： 0167-6997

Source： Investigational New Drugs, Vol.30, Iss.4, 2012-08, pp. : 1652-1659

Disclaimer: Any content in publications that violate the sovereignty, the constitution or regulations of the PRC is not accepted or approved by CNPIEC.

Previous Menu Next

Abstract

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.