Enzalutamide versus flutamide for castration-resistant prostate cancer after combined androgen blockade therapy with bicalutamide: the OCUU-CRPC study.

BACKGROUND: Before the androgen target therapy era, flutamide was widely used for castration-resistant prostate cancer in Japan. Enzalutamide is currently the recommended treatment; however, the efficacy and safety of enzalutamide and flutamide after combined androgen blockade therapy with bicalutamide, has not been compared. METHODS: Patients with castration-resistant prostate cancer who received combined androgen blockade therapy with bicalutamide were randomly assigned to receive either enzalutamide or flutamide. The primary endpoint for efficacy was the 3-month prostate-specific antigen response rate. This trial is registered with ClinicalTrials.gov (NCT02346578) and the University hospital Medical Information Network (UMIN000016301). RESULTS: Overall, 103 patients were enrolled. The 3- (80.8% vs. 35.3%; p < 0.001) and 6-month (73.1% vs. 31.4%; p < 0.001) prostate-specific antigen response rates were higher in the enzalutamide than in the flutamide group. The 3-month disease progression rates (radiographic or prostate-specific antigen progression) were 6.4% and 38.8% in the enzalutamide and flutamide groups, respectively [hazard ratio (HR): 0.16; 95% confidence interval (CI): 0.05-0.47; p < 0.001]; the 6-month rates were 11.4% and 51.1%, respectively (HR 0.22; 95% CI 0.09-0.50; p < 0.001). Enzalutamide provided superior prostate-specific antigen progression-free survival compared with flutamide (HR 0.29; 95% CI 0.15-0.54; p < 0.001). Median time to prostate-specific antigen progression-free survival was not reached and was 6.6 months in the enzalutamide and flutamide groups, respectively. CONCLUSIONS: As an alternative anti-androgen therapy in patients with castration-resistant prostate cancer who fail bicalutamide-combined androgen blockade therapy, enzalutamide provides superior clinical outcomes compared with flutamide. Enzalutamide should be preferred over flutamide in these patients.

[A case of castration-refractory prostate cancer showing marked decrease of serum PSA level after zoledronic acid treatment with estramustine phosphate and prednisolone].

A 66-year-old man was referred to our outpatient clinic for an elevated serum prostatic-specific antigen (PSA 4,319 ng/ mL). Magnetic resonance imaging (MRI) showed multiple metastatic lesions in the bones. The patient had received androgen deprivation therapy, but six months after treatment, he was diagnosed as having prostate cancer refractory to hormones. Combined treatment with docetaxel (DOC 30 mg/m²/week )and estramustine phosphate (EMP 560 mg/day) was initiated as first-line chemotherapy, but the treatment was discontinued because of side effects. Then, treatment with zoledronic acid was started(4 mg/4 weeks)and the PSA level decreased dramatically from 457.2 ng/mL to 5.5 ng/mL. Seven months after the diagnosis of CRPC, MRI showed a decrease ofbone metastases, and the PSA levels continued to decrease, eventually reaching 0.3 ng/mL. Zoledronic acid appears to not only show efficacy in preventing skeletal-related events, but has a potential antitumor effect in patients with metastatic CRPC.

A Case of Metastatic Urachal Carcinoma Treated With FOLFIRI (irinotecan and 5-Fluorouracil/leucovorin) Plus Bevacizumab.

A 68-year-old man was introduced to our hospital for the treatment of lung and mediastinum lymph node metastases that originated from an urachal carcinoma 4 years after a partial cystectomy. First-line chemotherapy with an S-1 and cisplatin combination was ineffective. The patient received FOLFIRI plus bevacizumab chemotherapy as salvage chemotherapy. Stability was achieved after eight cycles of FOLFIRI plus bevacizumab therapy. We conducted a biopsy of the metastatic tumor, and the pathology of the biopsy tissue was partially necrotic. To our knowledge, this case represents the first report of a metastatic urachal carcinoma treated with FOLFIRI plus bevacizumab.