Determination of enzalutamide long-term safety and efficacy for castration-resistant prostate cancer patients after combined anti-androgen blockade followed by alternative anti-androgen therapy: a multicenter prospective DELC study.

BACKGROUND: Alternative anti-androgen therapy has been widely used as a first-line treatment for castration-resistant prostate cancer, and it may affect treatment outcome of subsequent agents targeting the androgen receptor axis. We conducted the prospective observational DELC (Determination of Enzalutamide Long-term safety and efficacy for Castration-resistant prostate cancer patients after combined anti-androgen blockade followed by alternative anti-androgen therapy) study to evaluate the efficacy of enzalutamide in patients with castration-resistant prostate cancer who underwent prior combined androgen blockade with bicalutamide and then alternative anti-androgen therapy with flutamide. METHODS: The DELC study enrolled 163 Japanese patients with castration-resistant prostate cancer who underwent alternative anti-androgen therapy with flutamide following failure of initial combined androgen blockade with bicalutamide in multiple institutions between January 2016 and March 2019. Primary endpoint was overall survival. Administration of enzalutamide was started at 160 mg orally once daily in all patients. RESULTS: The rate of decline of prostate-specific antigen by 50% or more was 72.2%, and median overall survival was 42.05 months. Multivariate analysis revealed that higher pretreatment serum levels of prostate-specific antigen (≥11.3 ng/mL; P = 0.004), neuron-specific enolase (P = 0.014) and interleukin-6 (≥2.15 pg/mL; P = 0.004) were independent risk factors for overall survival. Fatigue (30.0%), constipation (19.6%) and appetite loss (17.8%) were the most common clinically relevant adverse events. The enzalutamide dose was not reduced in any patient under the age of 70, but adherence was decreased in those over 70. CONCLUSIONS: In the DELC study, the safety of enzalutamide was comparable to that in previous reports. Serum levels of neuron-specific enolase and interleukin-6 were suggested as prognostic factors for castration-resistant prostate cancer with potential clinical utility.

Mesotherapy with Bicalutamide: A New Treatment for Androgenetic Alopecia.

Bicalutamide is a selective androgen receptor antagonist. To date, it has been used orally with good efficacy results, but not in mesotherapy. In our center, we assessed whether patients undergoing bicalutamide mesotherapy showed positive responses and tolerated the local administration of bicalutamide. Six premenopausal women, with a mean age of 35.7 years and clinical diagnosis of Olsen Grade II or III female androgenetic alopecia accompanied by significant seborrhea were treated with 1 ml bicalutamide 0.5% mesotherapy. Three monthly sessions were performed. A subtle improvement in hair density was described after the third session. The overall satisfaction of the patients with the treatment was 6.3, on a scale of 1-10. Premenopausal women require several therapeutic approaches to combat severe androgenetic alopecia. Our data showed that bicalutamide mesotherapy was well tolerated and welcomed by the patients; we, therefore, provide a new tool for the management of this pathology.

Androgenic effects of aqueous and methanolic extracts of Ficus asperifolia in male Wistar rats.

BACKGROUND: Androgen deficiency is a clinical syndrome resulting from the inability of the testes to produce physiological levels of testosterone due to a disturbance occurring at one or more levels of the hypothalamic-pituitary-testicular axis. The present study was undertaken to evaluate the androgenic properties of aqueous and methanolic extracts of Ficus asperifolia on normal and castrated immature rats. METHODS: Normal rats were treated either per os with aqueous or methanolic extract of Ficus asperifolia (100 mg/kg or 500 mg/kg b.w.), distilled water (10 ml/kg b.w.), 5% Tween 80 (10 ml/kg b.w.) or subcutaneously with testosterone propionate (0.5 mg/kg b.w.). Castrated rats were treated with plant extracts (100 mg/kg b.w. or 500 mg/kg b.w.) alone or with the co-administration of plant extracts and testosterone propionate (s.c., 0.5 mg/kg b.w.) or bicalutamide (2 mg/kg b.w. per os). Animals were treated once a day during four weeks. Body weight growth and relative sexual organ weights were recorded at the end of each treatment. Some biomedical parameters were measured in the plasma (proteins, cholesterol), testes (cholesterol) and epididymis (proteins). RESULTS: In normal rats, Ficus asperifolia significantly (p < 0.05) increased the relative weights of the testes and all sexual-dependent organs whereas total testicular cholesterol concentration was significantly (p < 0.05) decreased. In castrated groups, treatment with Ficus asperifolia was followed by an increase in the sexual organ weights, epididymal protein and prostatic acid phosphatase concentrations. The co-administration of testosterone and plant extracts significantly (p < 0.05) increased the weight of accessory sexual organs and epididymal protein contents. In the presence of bicalutamide (an anti-androgen), the sexual stimulating activity of Ficus asperifolia was diminished with remarkable effects on vas deferens weight (p < 0.05), plasma (p < 0.01) and epididymal (p < 0.05) protein contents. CONCLUSION: Ficus asperifolia possesses androgen-like activity through possible stimulation of cytoplasmic and/or nuclear receptors by the bioactive compounds found in its extracts.