Treatment sequence in castration-resistant prostate cancer: A retrospective study in the new anti-androgen era

In recent years, abiraterone acetate (AA) and enzalutamide (EZL) have become available for the treatment of cancer. Prior clinical trials have demonstrated the benefits of these agents in males with castration-resistant prostate cancer (CRPC). The optimal sequencing of available therapies in the context of efficacy and known cross-resistance remains uncertain. Based on the mechanisms of action and accessible clinical data, AA and EZL may be indicated for the early stages of prostate cancer. Until clinical trials are conducted to determine the best treatment sequence, individualized therapy is required for each patient based on the clinicopathological characteristics. In the present study, 46 sequential patients (median age: 77, range 59-89; median serum PSA level: 56 ng/ml, range 1.5-3,211) with CRPC treated with EZL (160 mg/day) were retrospectively analyzed between June 2014 and July 2015 at the following institutions: Yamagata Prefectural Central Hospital (Yamagata, Japan); Yamagata Tokushukai Hospital (Yamagata, Japan); Ishinomaki Red Cross Hospital (Ishinomaki, Japan); Kan-etsu Hospital (Tsurugashima, Japan); Niigata Cancer Center Hospital (Niigata, Japan); Sakado Central Hospital (Sakado, Japan). A total of 18 patients were pre-treated with Docetaxel (DOC) and 28 patients were DOC-naïve. Once EZL therapy was initiated, increases in prostate specific antigen (PSA) levels were observed in 3/18 patients (17%) pre-treated with DOC and in 6/20 (30%) who were DOC-naïve. In total, 8/28 DOC-naïve patients were treated with AA without EZL. An increase in the PSA level was observed in only 1/8 (12%) cases following AA treatment in the DOC-naïve group. It was demonstrated that AA had a better efficacy in DOC-naïve patients. The efficacy of EZL was limited in AA-pre-treated patients following DOC administration.