Initial Experience of the Enzalutamide Treatment for Castration-Resistant Prostate Cancer

Abstract

(Objective) Enzalutamide is an oral androgen-receptor inhibitor that prolongs survival in men with castration-resistant prostate cancer (CRPC). We retrospectively evaluated clinical efficacy and safety of enzalutamide in CRPC. (Patients and methods) We reviewed clinical records of 73 patients who had received enzalutamide for the CRPC at Showa University and affiliated 7 hospitals. Enzalutamide was given at a dose of 160 mg/day, but some patients were treated at lower dose because of there age or poor performance status. Prostrate-specific antigen (PSA) response, prior docetaxel use and the previously administered agents were evaluated retrospectively. (Results) The median patients age was 77 years, the median Gleason score was 9 and the median PSA level at baseline was 26.9 ng/ml. The patients who had prior docetaxel use were 29 (39.7%) and the median of total docetaxel dose was 460 mg/body. The median number of total prior treatments (anti-androgens, Estramustine and steroid) was 3. Twenty seven (61.4%) patients with docetaxel-naïve achieved over 50% reduction of PSA level from baseline, but only 7 (24.1%) in patients previously treated with docetaxel. The most common adverse events included fatigue (24.7%), anorexia (24.7%) and the nausea (16.4%). We found a small proportion of responders to enzalutamide experienced a PSA flare. (Conclusion) Our results of the use of Enzaltamide for CRPC were similar with previous reports. PSA flare was found in some patients with CRPC who responded to enzaltamide. It should be noted that this possible PSA flare phenomenon.

Heterogeneous cancer-associated fibroblast population potentiates neuroendocrine differentiation and castrate resistance in a CD105-dependent manner

“…Notably, elevated PSA expression in 2D co-cultures of 22Rv1 with wild type fibroblasts treated with enzalutamide corresponded with elevated proliferation in 3D co-cultures of 22Rv1 and wild type fibroblasts treated with enzalutamide. A similar phenomenon has been seen in patients, where PSA flares result from enzalutamide treatment [46]. As demonstrated in our 3D cocultures, inhibition of both stromal and epithelial CD105 was necessary to suppress the proliferative effects of ADT on prostate cancer epithelia.…”

Efficacy and Safety of Enzalutamide in a Real-World Cohort of Japanese Patients With Castration-resistant Prostate Cancer

“…Our results suggest that ENZ is a welltolerated treatment option for CRPC in Japanese patients although physicians select its reduced doses. Although 71.4% of the patients in this study were administered reduced doses of ENZ due to their age and past medical history (e.g., cerebral infarction and polypharmacy), the efficacy of ENZ as represented by PSA response rates was found to be better than that reported in previous studies, where the standard dose of ENZ (i.e., 160 mg/day) was commonly used (2,3,6,7,10,11,16,25,(27)(28)(29)(30)(31)(32). One possible reason for the efficacy of reduced ENZ doses is that C SS, ENZ might suffice to treat CRPC.…”

“…Another possible reason for the efficacy of reduced ENZ doses is the low level of baseline PSA in our cohort. A previous study reported the baseline PSA level as one of the crucial factors in determining the effects of ENZ therapy on Japanese patients (11). That is, the median baseline PSA level in CRPC patients with a PSA decline of >50% was 23.4 ng/ml, which was relatively lower than that in cases with a PSA decrease of <50% (median, 41.5 ng/ml) (11).…”

“…However, adverse events (AEs) such as fatigue, constipation, and decreased appetite have been reported in most patients on a maintenance dose of 160 mg/day (2-11). Hence, physicians tend to select reduced doses of ENZ (e.g., 80 or 120 mg/day) in clinical practice (11)(12)(13)(14)(15)(16)(17).In a previous study, 16β-18F-5α-dihydrotestosterone positron emission tomography imaging showed a high affinity of ENZ for the AR at 60-360 mg/day (18). Furthermore, ENZ doses higher than 150 mg/day were found to have no additional effect on the magnitude of prostatespecific antigen (PSA) decline, despite resulting in higher steady-state trough plasma concentrations of ENZ (C SS, ENZ ) (18).…”

“…However, adverse events (AEs) such as fatigue, constipation, and decreased appetite have been reported in most patients on a maintenance dose of 160 mg/day (2-11). Hence, physicians tend to select reduced doses of ENZ (e.g., 80 or 120 mg/day) in clinical practice (11)(12)(13)(14)(15)(16)(17).…”