Combining a TKI with bicalutamide in men with CRPC


We have reported on a number of attempts to use tyrosine kinase inhibitors (TKIs) — alone or in combination with chemotherapy — in the treatment of men with castration-resistant prostate cancer (CRPC). Limited activity or efficacy has been reported to date.

Data from a small trial that combined the TKI sorafenib (Nexavar®) with bicalutamide appears to have been able to show some degree of clinical activity in men with CRPC. However, whether this activity would be sufficient to outweigh the side effects of sorafenib in clinical practice needs further research.

Beardsley et al. carried out a a multicenter, two-stage, Phase 2 clinical trial in chemotherapy-naïve prostate cancer patients who had a rising PSA but minimal symptoms after hormonal therapy. The patients were all treated with a combination of sorafenbib 400 mg twice daily and bicalutamide 50 mg once daily on a 28-day cycle.

The results of this trial were as follows:

  • The trial enrolled 39 patients in total.
    • 31/39 patients had evident metastatic disease (mCRPC).
    • 8/39 patient had no evident metastases (CRPC).
    • 38/39 patients were evaluable for PSA-related responses.
  • 18/39 patients (46 percent) demonstrated either a PSA response of ≥ 50 percent or stable disease at ≥6 months.
  • Reductions in PSA levels of ≥ 50 percent were observed in
    • 12/38 evaluable patients (32 percent) overall
    • 7/27 evaluable patients (26 percent) who had previously received antiandrogen therapy
  • Average (median) time to treatment failure was 5.5 months.
  • Significant adverse events (of Grade 3 or higher) included fatigue, skin rash, and hand-foot syndrome.

Although these data do suggest some level of activity of the combination of a TKI with an antiandrogen in men with CRPC, it is clear that such activity is associated with potentially serious side effects, and the potential impact on overall survival seems likely to be limited.

Sorafenib is already approved in the USA for the treatment of selected patients with advanced forms of kidney and liver cancers.

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