293 Background: In Asia, including Japan, combined androgen blockade (CAB) therapy with bicalutamide is widely used for metastatic prostate cancer. Alternative anti-androgen therapy (AAT) with flutamide (FLU) after CAB therapy with bicalutamide was common before the androgen receptor-targeted therapy era. The AAT response rate was 20–30%, and there is no evidence of prolonged overall survival (OS), but we have encountered effective clinical cases. Currently, two prospective clinical studies are ongoing, but this is the first retrospective study comparing FLU and enzalutamide (ENZ) for castration-resistant prostate cancer (CRPC). Methods: In our hospital, 55 patients were diagnosed with CRPC after CAB therapy and administered FLU or ENZ between May 2014 and December 2017. Patients with FLU failure then received ENZ. The study evaluation included 1) prostate-specific antigen (PSA) best response with initial therapy, 2) PSA progression-free survival with initial therapy (PSA-PFS), 3) PSA best response with ENZ therapy, 4) PSA-PFS of ENZ therapy (PSA-PFS-ENZ), and 5) OS. Results: As first-line CRPC therapy, patients received ENZ (n=29) or FLU (n=26). In the FLU group, 18 patients showed disease progression and then received ENZ. The PSA best response was statistically higher in the ENZ group. PSA-PFS was significantly statistically longer in the ENZ group (hazard ratio (HR) 1.85, 95% confidence interval (CI) 0.53–0.64, p=0.02). However, there was no significant difference in PSA best response with ENZ therapy and PSA-PFS-ENZ between the ENZ and post-FLU ENZ groups (HR 0.80, 95% CI 0.33–1.94, p=0.62) or in OS between the ENZ and post-FLU ENZ groups (HR 1.85, 95% CI 0.53–6.42, p=0.33). Conclusions: AAT with subsequent FLU after CAB therapy with bicalutamide may be suitable for some CRPC patients. (NCT02346578 and NCT02918968).
Time to progression to castration-resistant prostate cancer after commencing combined androgen blockade for advanced hormone-sensitive prostate cancer
